Pressure sensitive valves for extracorporeal pumping-3

ABSTRACT

The specification describes several uses for pressure sensitive valves during extracorporeal pumping in one embodiment, an improved pumping loop for a roller pump is used in an extracorporeal circuit with a pressure relief valve and pump tubing. The inlet and outlet of the tubing are connected respectively to the outlet and inlet of said valve via two 3 way connections, across the outlet of the pump. The pumping loop allows recirculation of pumped liquid between the inlet and outlet of the pump when the outlet pressure generated by said pump exceeds a set value thereby limiting the pump outlet pressure to the set pressure. The pressure relief valve can also be placed at the inlet if the pump to protect the circuit from excess negative pressure that the pump can generate. The pressure relief valve in combination with the pump loop provides an accurate means to dynamically set the occlusion of the tubing within the roller pump. Other applications for the pressure sensitive device include inline noninvasive pressure isolator, and pressure relief across other devices. Various designs are introduced.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation in part of allowed application U.S.Pat. No. 07/852,931 filed Mar. 13, 1992, U.S. Pat. No. 5,186,431, whichwas a continuation of U.S. Ser. No. 07/683,093 filed Apr. 10, 1992, nowabandoned, which was a continuation of U.S. Ser. No. 07/410,845 filedSep. 2, 1989, now abandoned, all of which were entitled "PressureSensitive Valves For Extracorporeal Circuits", application Ser. No.07/999,217, filed Dec. 31, 1992, U.S. Pat. No. 5,305,982, and allowedapplication U.S. Ser. No. 08/016,034, filed Feb. 10, 1993, U.S. Pat. No.5,429,483 both of which were continuation in part of the aforementionedU.S. Ser. No. 07/852,931, application U.S. Pat. No. 07/669,641 filedMar. 14, 1991, U.S. Pat. No. 5,215,450; entitled "Innovative PumpingSystem For Peristaltic Pumps"; and U.S. Ser. No. 07/876,627 filed May 6,1992 entitled "A Compact Low Cost Pressure Regulating System", nowabandoned, which contain similar pressure sensors and control systems,the disclosures of these applications being incorporated herein byreference thereto.

BACKGROUND OF THE INVENTION

The field of the invention is extracorporeal circulation of bloodoutside a patients' body, and particularly pressure sensitive devices tocontrol blood flow and pressure in the extracorporeal circuit whilereducing hemolysis.

DESCRIPTION OF THE PRIOR ART.

Blood is routinely pumped outside the body during dialysis,cardiopulmonary bypass and long term cardiac and/or respiratory support(e.g., extracorporeal membrane oxygenation, ECMO). Two types of pumpsare used: the roller and the centrifugal pump. With the roller pump, andto some extent with the centrifugal pump, a decrease in blood supply atthe pump inlet, without a concomitant decrease in pump speed, can causeexcessive suction leading to air embolism, thrombosis and damage by the"venous" cannula to the vessel's intima. Similarly, an obstruction atthe pump outlet can also result in excessive outlet pressure.

To overcome these potential dangers in closed systems such as ECMO ordialysis, bladders, placed at the inlet to the pump, collapse when inletpressure drops below atmospheric pressure, actuating a microswitch thatstops the pump and restarts when the bladder refills. This systemprovides no control over the degree of suction the pump generates. Theseknown prior art reservoirs (such as GISH BIOMEDICAL Santa Ana Calif.)are designed to operate horizontally, which forms a low flow regionwhere red cells tend to accumulate and thrombosis is likely to occur. Areservoir designed to eliminate gravitational accumulations wouldincrease clinical safety of bypass procedures.

Pressure measured directly with a liquid filled line which connects apressure transducer to the blood, requires a sterile transducer for eachapplication, provides no compliance for smooth pump operation, and hasblood stagnating in the pressure monitoring lines. Pressure measured viaa pressure isolator (e.g., Pressure Barrier Kit 3 made by American Omniof Costa Mesa Calif. 92626) allows for damping controlled by the amountof air on one of its sides but it has a much higher stagnant bloodvolume than direct measurements, thereby increasing the chances ofthrombosis. The only available compliance chamber is made of silicone,and its compliance or the pressure at which it collapses is notadjustable by the user. Also, with this chamber the blood sees threedifferent materials (PVC tubing to polycarbonate connector to siliconerubber) and three physical junctions, all of which contribute tothrombosis. Material and physical discontinuities also make it moredifficult, if not impossible, to apply a continuous heparin coating, ananticoagulant that inhibits thrombosis, to the circuit. U.S. Pat. No.4,515,589 and 4,767,289 (manufactured by Sarns/3M Corp. as the "SafetyLoop"), and 4,650,471, describe devices to be used with the roller pumpthat prevent too much suction. The former provides no adjustment overthe pressure about which flow is controlled. The '471 patent describesadjustment capabilities for the inlet, but neither provides relief foroverpressurization at the outlet of the pump.

The only pressure sensitive valve that is known to be used clinically inthe extracorporeal circuit is the one incorporated at the inlet to the"Safety Loop" mentioned above. Its assembly is labor intensive andrequires multiple parts. In addition, its housing is exposed toatmosphere and provides no mechanism to adjust the interluminalpressure. Senko Medical Instrument Mfg. Co., LTD. of Tokyo, Japanmanufactures a pressure relief valve intended for dialysis that isplaced at the outlet of an ultra-filtration device to maintain itspressure constant independent of the flow. It is made by sealing a thinwall plastic diaphragm between the two thicker walls of a tube, thediaphragm separating the pressure port and the blood path. This valve,however, has physical discontinuities along the seal between the thinand the thick wall tubing, creating areas of stagnation which are proneto thrombus formation. In addition, the housing is not optically clear,which prevents the user from observing whether the valve is open orclosed, and the pressure port is perpendicular to the thin membrane,again reducing the clarity required for observation of valve open state.

In the medical field, valves known as Starling resistors, are made of athin walled sleeve and require negligible transwall pressure differenceto close them. They have been suggested for use to maintain or adjustpressure, (Robert Rushmore: Control of Cardiac Output, in Physiology andBiophysics 19th edition Ruch TC and Patton HD editors, WB Saunders Co.Phil. 1965).

These valves made of a sleeve sealed in a housing with means topressurize the interluminal space (the space between the housing and thesleeve). Pressure applied to the interluminal space acts upon the wallof the sleeve forcing the opposite walls of the sleeve to meet and closeshut. This external force on the wall is counteracted by the pressurewithin the lumen of the sleeve which tends to keep the walls apart. Itis the net force of these two vectors that determines whether the sleeveis opened, closed or in between.

In industry, these valves are used as ON/OFF valves or as adjustableresistors known as pinch valves. Pinch valves are also used to adjustthe resistance to flow using an external roller that pinches and thuscontrolling the degree of closure of the sleeve. If the wall of thesleeve is made sufficiently thin, the valve can also be used to transferthe pressure of the fluid within the sleeve to the interluminal spacewithout significant changes in the transducer pressure. Thus, thesedevices can transmit the pressure of a fluid that may be corrosive to apressure gauge while isolating the pressure gauge from the fluid.

U.S. Pat. No. 4,767,289 teaches that a Starling valve may be made of athin wall tubing, each end of which is sealed to a rigid connector whichin turn is sealed to the housing, providing a flow through chamber. U.S.Pat. No. 4,515,589 teaches that the walls of the thin wall tubing mayextend beyond the housing, be folded upon themselves and sealed over theexternal wall of the housing. These techniques have one or more offollowing disadvantages: 1) the thin wall tube is stressed over theedges of the housing, 2) the assembly requires sealing the thin walltube to the connectors, 3) the discontinuities of the valve at theconnection site between the thin wall and the thick wall tubing cancreate turbulence and trapped vortices, a leading cause of thrombusgeneration, 4) the assembly is labor intensive and requires multipleparts, and 5) control over the interluminal pressure with presentsystems is provided by a cumbersome and bulky combination requiring acompliance chamber, a pressure manometer and interconnecting tubing.

U.S. Pat. No. 4,250,872 by Tamari illustrates a valve made of unitarytubing, a portion of which has been expanded and thinned to allow easycontraction by external fluid pressure. However, the way this valve wasmade, it could not fully close (as illustrated in FIG. 5) nor was itpreformed to close completely. None of the aforementioned devices aresuggested for use directly at the pump outlet, a placement that allowsthe greatest protection for the entire circuit.

Inflatable elastomeric bladders have been used for pressure indicationand regulation (e.g., part no. BSVD-300, Shiley, Laboratories, Irvine,Calif. , and Buckels U.S. Pat. No. 3,993,069). The pressure-volumecharacteristics of these balloons have a high or low frequencyhysteresis, and/or the highest pressure occurs upon initiation ofinflation and thereafter it decreases (e.g., see FIG. 1 of U.S. Pat. No.3,993,069, and FIG. 6 of Tamari's U.S. Pat. No. 5,013,303). The Shileydevice is a spherical balloon and therefore upon inflation its size, butnot its shape, changes. Neither device allows the user to adjust thepressure. It would be useful to have a pressure regulator with a shapechange which indicates pressurization more clearly. It would also be ofgreat advantage to provide the user with the means to adjust the maximumoutlet pressure of pumps and incorporate inexpensive means to measurenoninvasively the pressure of the pumped fluid.

Hemolysis by roller pumps is due to crushing of blood cells between thewalls of the tubing being squeezed and/or high shear rates possible withretrograde flow through nonocclusive tubing. Pump occlusion is set bymeasuring the drop rate of a column of liquid at the outlet of a stoppedpump. Drop rates anywhere from 1 to 40 cm/min per 100 cm pressuredifference are reported in the literature. The drop method has fivemajor disadvantages: inaccuracy because of relatively large variation intubing wall thickness (±0.003"), unequal extension of the two rollers,off center roller rotation, pump raceways that are not truly circularand, during fast drop rates, the pressure decreases as the liquid falls.Thus, proper occlusion setting requires averaging of multiple readingswhich is a time consuming effort. Although it is reported by Bernsteinand Gleason (Factors influencing hemolysis with roller pumps, Surgery,61:432-442, 1967) and Noon et. al. (Reduction of blood trauma in rollerpumps for long-term perfusion, World J. Surgery 9:65-71, 1985) thathemolysis increases as the occlusion is increased, for very nonocclusivesettings the drop rate is too fast to measure accurately. Others havesuggested that roller occlusion be set by measuring a pressure drop atthe outlet of the pump. With this method, the pump outlet is clamped,the pump is rotated to increase the pressure to the desired level, thepump is then stopped, and the rate of pressure drop measured. Occlusionsetting by this method is very dependent on the compliance between thepressure transducer and the roller occluding the tubing: the larger thecompliance the lower the occlusion. Both aforementioned methods use astationary pump, referred to hereafter as static tests which rely on ameasurement taken from a single point along the pump raceway and from asingle roller to determine occlusion. It may be that one of the reasonsthat users generally do not set the pumps in a less occlusive manner, isthe difficulty in doing so accurately. It would be of great clinicaladvantage to be able to provide control over the maximum pressure in anextracorporeal circuit and the maximum suction the patient is exposedto, as well as to provide a simple means to enable the user to set thepump nonocclusively and provide a standard roller pump with theadvantages of a centrifugal pump without its associated high costs.These can be done with pressure sensitive valves and appropriate controldevices.

SUMMARY OF THE INVENTION

The present invention is a unique pressure sensitive device, which isused in combination with an extracorporeal circuit to control flow,pressure and blood handling devices therein. In one embodiment, thepressure sensitive device and pump tubing are interconnected via 3-wayconnectors, to limit excess pump pressure in a peristaltic pump used forextracorporeal circulation. In another combination, a pressure sensitivevalve that is normally open is placed at the inlet to the roller pumpand is used to limit the negative pressure applied to saidextracorporeal circuit. The device can also be used to accurately setthe occlusion of said peristaltic pumps as well as to measure bloodpressure noninvasively.

The present invention may be formed in various embodiments eachconsisting of a polymeric tubing with at least one flexible thin wallsection, said section sealed within a housing with a port to form afirst pressure chamber. The thin wall section is designed to reduce thepressure required to move the thin wall section and can be used forvarious purposes. Its nominal diameter may be greater than, equal to orsmaller than the inside diameter of the tubing it is formed in orconnected to. In one embodiment, the thin wall section can, for example,be incorporated within a housing to form a pressure relief valve. Thetubing for the pressure relief valve is preferably made of a single,indefinite length, uniform, smooth, fissureless, thermoplastic,elastomer which is flexible and clear, a section of which has beenprocessed and sealed within the housing to form first pressure chambertherebetween. The pressure in the first pressure chamber is adjusted viaa port. Thus, when the pressure in the first pressure chamber is greaterthan the pressure inside the thin wall processed section, the valve isclosed, and when the pressures are reversed, the valve is open. When thepressure relief valve is placed between the inlet and outlet of a pump,the user can adjust the maximum outlet pressure of the pump by adjustingthe pressure applied to the first pressure chamber. When the pump outletpressure reaches the set pressure, the pressure relief valve opens,allowing excess pressure to be relieved by recirculating some of theflow. The pressure in said first pressure chamber can, for example, becontrolled by an elastic balloon or by other mechanisms to be describedherein. The pressure sensitive device can also be used to accurately setthe occlusion of peristaltic pumps as well as to transmit pressure fromthe first pressure chamber, to thereby allow noninvasive inline pressuremeasurement. In other designs to be described, the processed section,when having an enlarged diameter, can be used as an inline reservoirwith an adjustable compliance providing both noninvasive pressuremeasurement and an inline reservoir.

In another embodiment, the present invention may be integrally isincorporated into blood tubing intended for use in an extracorporealcircuit to regulate blood flow therethrough. This embodiment uses alength of unitary extracorporeal tubing interconnected in theextracorporeal circuit. The tubing has a first outer diameter and afirst wall thickness, with a thin wall portion defined intermediate theends of the tubing. The device also includes a housing having an innerdiameter at each end thereof which snugly engages the tubing. Thehousing has a port formed therein which communicates with a sealedinterluminal chamber formed between the thin wall tubing portion and thehousing. Each end of the housing extends beyond the thin wall portion toengage the tubing along the first outer diameter.

A pressure regulating means is then connected to the port, to provide apredetermined pressure response to the blood flow. A pressurized fluidbetween the pressure regulator means and the thin wall portion willactuate the valve when the interluminal pressure varies from theintercorporeal pressure within said thin wall tubing by at least theamount required to overcome the elastic force of the thin wall tubing.It is particularly intended to be incorporated in an extracorporealcircuit for circulation of blood, wherein the circuit has a plurality ofblood treatment devices and a plurality of blood compatible tubingmembers with connectors therebetween for circulation of bloodtherethrough.

In the present invention a pressurized elastic sleeve may be used toregulate the pressure and provide a predetermined pressure response forthe pressure sensitive devices. The regulated pressure may be positiveor negative pressure.

The present invention may also be formed as an improved pump loop foruse with a roller pump in extracorporeal circulation. When used in thismanner, the loop includes a first tubing segment for insertion in aroller pump for pumping extracorporeal fluids therethrough. The tubinghas a pump inlet and a pump outlet and a shunt tubing for fluidconnection of the pump outlet to the pump inlet. A pressure relief valveis then provided for closing the shunt tubing below a predeterminedpressure. The pressure relief valve may further include a thin walltubing portion formed in the shunt tubing between said pump outlet andsaid pump inlet, or may include a thin wall section mounted between saidpump outlet and said pump inlet, either one of which is surrounded by ahousing.

The present invention may also be formed as a system for regulatingpressure in an extracorporeal circuit, wherein the system includes anextracorporeal circuit for circulation of blood through a plurality ofdevices for circulating and treating blood, wherein each device has ablood inlet side and a blood outlet side. A shunt tubing is provided tobridge one of the devices by connecting the outlet side to the inletside. A pressure responsive valve is mounted in the shunt to normallyclose the shunt tubing below a predetermined pressure. The pressureresponsive valve will thus open to allow blood flow through said shuntwhen the blood pressure in the shunt is greater than said predeterminedpressure.

Alternately, the pressure responsive valve may be positioned at theinlet side of the pump to prevent excess suction that can be generatedby the pump for reaching the patient. The pressure responsive valve isthen formed to be normally open above a predetermined pressure at saidpump inlet and closed when the pressure at the pump inlet drops belowthe predetermined pressure.

The invention may also be used to set pump occlusion for extracorporealroller pumps having at least two rollers for sequentially occluding atubing member to pump an extracorporeal fluid therethrough, wherein ashunt tubing member interconnects the pump outlet and the pump inlet. Apressure relief valve then closes the shunt tubing member below apredetermined pressure. A means is provided for indicating fluid flowfrom the pump outlet to the pump inlet, and a clamp is used to clamp thepump outlet distal to the tubing member while the pump occlusion isadjusted. The desired occlusion is then obtained by adjusting thesetting of the adjustable roller to generate a pump pressure essentiallyequal to the predetermined pressure.

The present invention may also be used to provide a noninvasive pressuremonitoring system for pumps. This combination includes a length oftubing having at least one thin wall portion, a pump having a drivemeans for pumping fluid through the tubing and a pressure isolatingchamber surrounding the thin wall portion, the chamber having amonitoring port defined therein which is connected to a transducermeans. The transducer means is then connected to the drive means forcontrolling the speed of the pump, and varies pump speed when thepressure in the tubing varies from a predetermined value.

The present invention also includes a noninvasive pressure monitoringsystem for roller pumps. This system includes a length of polymeric,unitary, fissureless tubing having first and second thin walled portionswith a roller pump engaging section therebetween and a roller pumphaving an adjustable drive means. The inventor also includes first andsecond pressure isolating chambers surrounding said first and secondthin walled portions respectively. Each of the first and second chambershas first and second respective monitoring ports defined therein. Avariety of means are then connected to the monitoring parts.

The present invention also includes an inline reservoir for use in anextracorporeal circuit to provide compliance for blood flowtherethrough. The reservoir includes a length of unitary extracorporealtubing, interconnected in the extracorporeal circuit, with a first outerdiameter and first wall thickness, and an enlarged thin wall portiondefined intermediate the ends of the first wall tubing. A housing isprovided which snugly engages the outer diameter of the tubing. Thehousing has a port therein, which communicates with a sealedinterluminal chamber formed between the enlarged thin wall tubing andthe housing. Each end of the housing extends beyond the enlarged thinwall portion to engage the tubing along its outer diameter. The chambermay then be pressurized to a predetermined positive or negative value topromote compliance in the desired operating range.

The present invention may also be used to provide an adjustable pressureregulator for supplying a static pressure to a pressure sensitive devicewhich is to be pressure regulated. The regulator includes a firstisolating chamber, with the chamber having a first flexible diaphragmfor separating a fluid chamber having a fluid to be pressure regulatedfrom a first liquid chamber. The regulator also includes a secondisolating chamber, with the second chamber having a second flexiblediaphragm for separating a second liquid chamber from a third chamber. Aconduit connects the first liquid chamber and the second liquid chamberto form an interconnected liquid column. A tubing member connects thefluid to be pressure regulated to the first isolating chamber whereby astatic pressure is added to the fluid to be pressure regulated by thestatic pressure of the liquid between the first and second diaphragms.

The invention also includes an inline extracorporeal noninvasive flowmeter. The flow meter includes a first length of unitary elastomerictubing having a first and second thin wall portion defined therein, witha known flow resistance therebetween and first and second pressureisolating chambers surrounding the first and second thin wall portionsrespectively. Each of the first and second pressure isolating chambershas a first and second respective sampling ports defined therein whichare connected to a means for measuring the pressure differential betweenthe first and second sampling ports, whereby the extracorporeal flow maybe calibrated from the measured pressure differential and the known flowresistance.

It is the objective of the present invention to modify, improve andprovide a new overall system that can be used to provide an adjustablepressure relief valve and a suction shut off valve, both of which can becontrolled with simple compact pressure/suction control device.

A further objective of the present invention is to provide a new overallsystem that provides the standard roller pump with the advantages of thecentrifugal pump with the added advantages of enabling the user toadjust the maximum outlet pressure and minimum inlet pressure, each ofwhich can be controlled with a simple compact pressure/suction controldevice, at a significant reduction in cost.

It is also an objective of the present invention to modify, improve andprovide a valve to accurately control resistance to blood flow in anextracorporeal circulation.

A further objective of the present invention is to form anextracorporeal circulation regulating valve wherein it replaces standardshunts that are presently clamped (e.g., arterio-venous or arterialfilter shunt).

A further objective of the present invention is to provide a pressurerelief valve that provides easy visualization of both its closed andpressurized states.

A further objective of the present invention is to provide a pressurerelief valve with vibration or flutter to act as an alarm. Alternately,the valve may be designed to eliminate flutter or vibration due to flowthrough it.

A further objective of the present invention is to provide a pressurerelief valve that is blood compatible, that will withstand high internalpressures and that may be easily manufactured.

Another objective of the present invention is to have a thermoplastic,extruded tubing for conventional roller pumps (peristaltic pumps) thatincorporate inexpensive means to measure non invasively and/or controlthe pressure of pumped fluid at the inlet and outlet of said pump and/orthe flow directed to the patient.

Another objective of the present invention is to have a device thatcould be used to measure and control the minimum inlet and maximumoutlet pressure of an extracorporeal pump without additional risk ofthrombosis present with current systems.

Another objective of the present invention is to provide a single devicewhich will facilitate noninvasive pressure measurements, providepressure control and form a blood reservoir from a single length ofstandard extracorporeal tubing.

Another objective of the present invention is to reduce the probabilityof clotting by increasing blood flow through the circuit, especiallythrough the oxygenator when flow to the patient is low.

Another objective of the present invention is to provide a device thatwould limit the outlet or inlet pressure when used with a centrifugalpump. The device limits the recirculation of blood within the pump thatmay occur at low flow rates and high pressures. This enables the systemto recirculate the blood, reducing the exposure time of the blood tohigh shear within the pump.

Another objective of the present invention is to provide regulation ofpositive or negative pressure within an extracorporeal circuit.

A further objective of the present invention is to modify, improve andprovide a flow through (an inline) isolator between the blood andpressure monitors and/or other devices that require blood pressure(negative or positive) to function and/or control without contaminatingthe blood.

A further objective of the present invention is to form anextracorporeal circulation regulating valve which replaces standardshunts that are presently clamped, (e.g., arterio-venous or arterialfilter shunt). The sleeve of the valve is affixed directly to alreadyused "Y-connectors" and sealed within an elastic or flexible housing soas to allow it to be occluded by mechanical clamping, as with a tubingclamp.

As part of an overall system to improve peristaltic pumping of blood,the present invention features a simple pressure control box thatutilizes the inlet and outlet pressure monitoring capabilities of thedevice to provide flow regulation.

A further objective of the present invention is to provide a flowthrough blood reservoir that can be used to measure and control theblood pressure within it noninvasively.

A further objective of the present invention is to provide a mechanicalcontrol system to adjust the maximum outlet pressure and minimum inletpressure without changing the pump speed, while allowing clearobservation of the open state of the flow control means.

A further objective of the present invention is to make the devicesdisposable, atraumatic, biocompatible, long lasting, with predictableand clinically useful functional characteristics.

A further objective of the present invention is to incorporate anappropriate resistance at the valve outlet to reduce trapping shearconcentrations.

Another objective of the present invention is to provide a fissurelesscontinuous length of flexible, blood compatible, polymeric tubing with asmooth inner surface throughout for either the valve or reservoirs topromote the ease of heparin coating and to improve blood compatibility.

Other objectives, features and advantages of the present invention willbecome apparent by reference to the following detailed description ofthe presently preferred, but nonetheless illustrative, embodimentsthereof with reference to the accompanying drawings wherein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic representation of a system according to thepresent invention and showing particularly pressure sensitive valves invarious locations of a clinical cardiopulmonary bypass circuit, eachvalve with an associated pressure control device for controlling thevalve according to its respective function;

FIG. 2a is a sectional view of valve 531 taken between lines 2 and 2' inFIG. 1 illustrating one preferred embodiment of a pressure sensitivevalve;

FIG. 2b is a schematic illustrating compliance chamber and pressuremonitor that can be used to pressurize a pressure relief valve accordingto the present invention;

FIG. 3 is a transverse sectional view taken along lines 3 and 3' in FIG.2a showing the expanded and contracted configuration of the inner thinwall tubing;

FIG. 4 is a transverse sectional view taken along lines 3 and 3' in FIG.2a showing another preferred cross section of a pressure relief valve ina contracted state modified to form two bleed channels;

FIG. 5a is a schematic illustrating the combination of the pressurerelief valve that is normally closed, the pump tubing as installed in aconventional roller pump, the 3-way connectors and their respectiveinterconnection according to the present invention;

5b is another view of the valve shown in FIG. 5a illustrating atransverse sectional view of one preferred relative orientationproviding easier debubbling of said valve;

FIG. 5c is another view of the valve shown in FIG. 5a illustrating atransverse sectional view of one preferred relative orientation betweenthe flattened portion of pressure relief valve and the pressureindicator that maximizes user view of valve open state and elasticsleeve pressurized state;

FIG. 5d is a schematic illustrating the combination of a pressure reliefvalve installed at the outlet of a centrifugal pump, a 3-way connectorand a cardiotomy reservoir with their respective interconnectionaccording to the present invention;

FIG. 6 is a transverse sectional view taken along lines similar to 3 and3' in FIG. 2a showing a housing with improved optical characteristicsand a pressure relief valve rotated 90°. The thin wall tubing thereinhas a single bleed channel;

FIG. 7a illustrates the optical characteristics of a side view of apressure relief valve in three stages: completely closed (aa), justopening (bb), and open (cc);

FIG. 7b is the top view of the pressure relief valve shown in FIG. 7aillustrating the optical characteristics of said valve when it iscompletely closed (aa), just opening (bb), and open (cc);

FIG. 8 is a sectional view of a preferred embodiment of a pressureregulator for valve 441 illustrated in FIGS. 5(a) and 5(d) utilizing anelastic cylindrical balloon, sealed to a check valve with a Luerconnection;

FIG. 9 illustrates the relationship between pressure and volume for atypical elastic sleeve, such as that illustrated in FIG. 8, saidrelationship being useful for adjusting control pressure for a pressurerelief valve;

FIG. 10 is a sectional view of another preferred embodiment of aregulator incorporating a pressure indicator for controlling eithernegative or positive pressure applied to the pressure relief valve,utilizing a spring in a sealed flexible polymeric envelope;

FIG. 11a illustrates a pressure relief valve utilizing the combinationof a thin wall tubing a housing and Y-connectors for the valve assembly;

FIG. 11b is an enlarged view illustrating a detail of a section of thepressure relief valve shown in FIG. 11a;

FIG. 12 illustrates an embodiment of a pressure relief valve thatutilizes a thin wall sleeve attached to the housing by way of spacers;

FIG. 13 illustrates an alternate embodiment forming a first pressurechamber for a pressure relief valve utilizing spacer sleeves to sealbetween housing and unitary tubing;

FIG. 14 illustrates an alternate embodiment forming a first pressurechamber for a pressure relief valve utilizing a thermoplasticcylindrical housing sleeve that is heat sealed to unitary tubing on eachside of thin wall portion as well as to a pressure control line;

FIG. 15 illustrates a cross sectional view of a pressure relief valveconstructed with a standard connector as a rigid housing forming a firstpressure chamber by folding a thin wall tubing over the said connectorends;

FIG. 16a illustrates a cross sectional view of a pressure relief valveconstructed with a thermoplastic housing sealed to a membrane to form afirst pressure chamber and a blood path;

FIG. 16b illustrates a cross sectional view of a pressure relief valveconstructed with a thermoplastic housing with an alternate control portconstruction;

FIG. 16c illustrates cross sectional top view of the pressure reliefvalve shown in FIG. 16b taken along section line 16-16' with a pressureport oriented parallel to the thin wall section;

FIG. 17a illustrates a cross sectional view of a pressure relief valvewith pressure regulation provided by an elastic clamp;

FIG. 17b illustrates a cross sectional view along line 17-17' of thepressure relief valve shown in FIG. 17a;

FIG. 18a illustrates a cross sectional view of a pressure relief valvewith pressure regulation provided with another form of an elastic clamp;

FIG. 18b illustrates a cross sectional view along line 18-18' of thepressure relief valve shown in FIG. 18a;

FIG. 19 illustrates a cross sectional view of a pressure relief valvewith pressure regulation provided with an adjustable spring loadedclamp;

20a illustrates a cross sectional view of a pressure relief valve withpressure regulation provided with another type of an adjustable springloaded clamp;

FIG. 20b illustrates a side view of the pressure relief valve andadjustable spring loaded clamp shown in FIG. 20a;

FIG. 21a illustrates another embodiment of a pressure relief valvewherein an extruded tube with a thin wall separating the blood flow pathand pressure regulating chamber is used to form the pressure sensitivedevice;

FIG. 21b is a cross sectional view of a pressure relief valve as shownin FIG. 21a taken along line 21b-21b';

FIG. 21c illustrates another embodiment of a pressure relief valve,wherein a coextruded tube with a thin wall is formed inside the tube toseparate the blood and pressure regulating chambers;

FIG. 22 shows one combination of a pressure relief valve that isnormally open and a roller pump used for suction, wherein the pressurerelief valve is used to limit suction applied to patient and/or setocclusion of said pump;

FIG. 23 is an illustration of a unitary pump tubing incorporating twoinline pressure sensitive devices, a reservoir and pressure transmitterat its inlet and a pressure isolator at its outlet the tubing beingshown in combination with an electromechanical device which used tolimit inlet suction and outlet pressure;

FIG. 24 illustrates a cross sectional view of an accurate positive ornegative pressure regulator combined with a pressure relief valve toassure that the pressure on the blood side of a microporous oxygenatoris always greater than the pressure on the gas side of the oxygenator;

FIG. 25 illustrates a unitary tube incorporating two independentpressure isolators separated by a tubing section with a known resistanceto flow used to determine flow;

FIG. 26 is a sectional view of a preferred embodiment of a negativepressure regulator utilizing an elastic cylindrical balloon, sealed to aLuer connection;

FIG. 27 illustrates the relationship between pressure and volume for atypical elastic sleeve, such as that illustrated in FIG. 26, saidrelationship being useful for adjusting negative control pressure for apressure relief valve.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Reference should now be made to the drawings wherein the same last twodigits of the reference numerals are used throughout to designate thesame or similar parts. It should be noted that the use ofcardiopulmonary bypass, as shown in FIG. 1, is for descriptive purposes,and should not be taken as a limitation to the use of the devicesdescribed thereafter.

A typical extracorporeal circuit to which pressure sensitive valves inaccordance with the present invention may be applied is illustrated inFIG. 1 as including a section of tubing 23 inserted at one end by meansof a cannula (not shown) in the vena cavae for obtaining venous bloodfrom the heart (not shown) of patient 2. Tubing 23 is coupled, as anexample, to a venous reservoir 3. The blood is drawn from the venousreservoir 3 via tube 35 by roller pump 4 and pumped through a membraneoxygenator 5 wherein oxygen is supplied to the blood and carbon dioxideremoved. The blood from the oxygenator is then conducted by means oftubing 57 to arterial filter 7 and then via tubing 72 and an arterialcannula (not shown) back to the patient. Blood spilling into the chestcavity (not shown) is collected via unitary tubing 28 by suctiongenerated by roller pump 9 and pumped into cardiotomy reservoir 8 fromwhich it flows by gravity drainage through unitary tubing 83 into venousreservoir 3. Pressure sensitive valves may be placed in variouslocations in the extracorporeal circuit depending on the desiredpurpose. Valves are shown as 281, 981, 231, 341, 441, 451, 531, 571 and771 in FIG. 1.

A volume sensitive valve 231 is inserted between the patient and theinlet to venous reservoir 3 in unitary tubing 23. As will be hereinafterexplained in detail, by adjusting the interluminal volume or pressure ofvalve 231, it is possible to vary the resistance to modulate the flowthereby controlling the venous blood flow to the venous reservoir. Theinterluminal volume can be adjusted by adding or removing volume withcompressible or incompressible fluid. The use of incompressible fluidprovides more accurate control over the absolute opening of the valve.Utilizing sterile physiological solutions, as for example saline, as theincompressible solution also provides a safety feature: should the thinwall section develop a leak, the blood would not be contaminated norwould it be exposed to a gas that could cause gas embolus.

A pressure sensitive valve 341, inserted between reservoir 3 and theinlet to roller pump 4 in unitary tubing 35, protects against pumpingair to the patient should the reservoir empty and may also be used tolimit the maximum negative pressure applied to the blood as described inreference to FIG. 22. As will be hereinafter explained in detail, thisis achieved by having the valve collapse to a closed state when theblood pressure decreases below a preset value usually equal to hydraulicpressure exerted by the minimum acceptable blood level of venousreservoir 3. Valve 341 reopens when the blood pressure reaches a valuegreater than the preset value of the valve. It should be noted that avolume sensitive valve is similar to a pressure sensitive valve exceptthat the wall of the former may be thicker.

In the circuit shown in FIG. 1, it is necessary to prevent the entry ofair into the blood stream through the micropores of a membraneoxygenator 5 if the gas pressure is greater than the blood pressure.This can occur when the membrane oxygenator is above the venousreservoir 3 or the gas outlet port is obstructed. To prevent the former,presently the venous reservoir 3 must be positioned above the membraneoxygenator, thus limiting venous drainage. An additional 20 to 30%increase in venous drainage could be provided if the reservoir could beplaced below the membrane oxygenator. This can be achieved by placing apre pressurized pressure relief valves 451 and 571 at the inlet andoutlet of the membrane oxygenator 5. Pressure sensitive valve 451 asdescribed hereinafter, is incorporated in unitary tubing 35 between pump4 and the inlet to oxygenator 5. Pressure sensitive valve 571 isincorporated into unitary tubing 57 at the outlet of oxygenator 5. Thevalves open when the inlet blood pressure is greater than the hydraulicheight between the reservoir and the oxygenator. Thus, the two valvesisolate the microporous oxygenator from the venous reservoir and assurethat the pressure on the blood side of the microporous oxygenator isalways above atmospheric pressure on the gas side. This has theadvantage of being able to place the venous reservoir below the membraneoxygenator thereby providing greater gravity drainage presently notpossible with known prior art devices. A pressure isolation feature ofvalve 451 also provides means to measure arterial line pressure withoutdirect blood contact.

A pressure sensitive valve 531, acting as a pressure relief valve, isincorporated into unitary tubing 53 between the inlet and outlet ofarterial pump 4, shown connected at outlet tube 57 and venous line 23,prevents accidental overpressurization at the outlet of pump 4. The useof this valve provides additional clinical advantages not possible withthe standard roller pump. For example, at the end of the operation whenthe patient is off cardiopulmonary bypass (CPB), blood is administeredto the patient by pumping from the oxygenator through the arterialcannula. The surgeon tells the perfusionist to infuse 100 ml, theperfusionist unclamps the arterial line, turns the pump till 100 ml areinfused and then shuts the pump off and reclamps the arterial line. Thisprocedure requires coordination with the surgeon depending on theperfusionist for accuracy. With pressure relief valve 531, as the shuntbetween the arterial and venous line, the roller pump can be left oncontinuously and the surgeon can control blood administration directlyby opening and closing a tubing clamp himself. Another advantage is,that in the event arterial filter 7 plugs up, valve 531 would open toprevent over pressurization of the arterial line and in addition woulddivert the blood from the patient back to the venous line. This isespecially useful if the build up in pressure is due to thrombus, aclamped filter outlet, or an obstructed arterial cannula. It should benoted that should valve 531 open during CPB the blood volume at theinlet to the pump will tend to increase. This increase would beunlimited with an "open system" (e.g., bubble oxygenator) but would belimited to the capacity of the inlet reservoir (e.g., venous reservoirof membrane oxygenator). This implies that the use of a recirculatingvalve will benefit from a means to indicate that the valve is open.Reduction in flow to the patient can be indicated by reduction in thearterial pressure of the patient, a flow meter attached to the arterialline between valve 531 and the patient, or an alarm to indicate wheneverthe valve opens, as described hereinafter.

A pressure sensitive valve 441, incorporated into unitary tubing 44 andplaced directly between the outlet and inlet of arterial pump 4 to forma pumping loop as shown in FIGS. 5a-5d, functions in an identical manneras valve 531 but its location provides additional protection againstexcess pressurization for devices between pump 4 outlet andrecirculation line 53 containing valve 531. Either valve 441 or valve531 can be used to set the occlusion of arterial pump 4 as explainedwith respect to FIGS. 5a and 7a-b.

A pressure sensitive valve 771 can also be incorporated across the inletand outlet of the arterial filter in unitary tubing 77 to prevent overpressurization of the arterial line due to a plugged filter.

A pressure sensitive valve 281, incorporated between the patient's chestcavity or a vented heart chamber and the inlet to suction pump 9, actsas a suction control valve and protects the patient 2 from excessnegative pressure. This valve stays open as long as the blood pressurebetween the pump and the patient is higher than that set by the user ormanufacturer. Valve 281 can also be used to set the occlusion of suctionpump 9 as explained with respect to FIG. 22.

A pressure sensitive valve 981 may be incorporated into unitary tubing28, between roller pump 9 and the inlet to cardiotomy reservoir 8, andopens only if the blood pressure is above the interluminal pressure. Ifthe interluminal pressure is maintained slightly positive, and thecardiotomy reservoir 8 is open to atmosphere, then if suction pump 9,when used for venting one of the heart chambers, is accidentallyreversed, valve 981 would close, preventing pumping air back to thepatient.

As described, the pressure sensitive valves of the present invention canbe used to: open and relieve excess pressure, close when the pressuredrops too low, adjust resistance to flow and transmit a pressure signalacross its wall. Each application may require a slightly different meansfor setting the predetermined pressure, the basic valve construction canremain the same. The specific operation, related design and differentapplications of each valve is hereinafter described.

FIG. 2a illustrates one presently preferred embodiment of the pressuresensitive valve which is illustrated in use in FIG. 1 as 231, 281, 341,441, 451, 531, 571, 771, and 981. Valve 531 includes a unitary tubingmember 53 passing through a generally cylindrical or elliptical housingor enclosure 232 which is nonelastic in construction using a clearthermoplastic material such as polycarbonate, polyvinylchloride, PETG orthe like. Tubing member 53 preferably consists of a continuous length ofblood compatible, flexible, polymeric, transparent material having asmooth fissureless inner surface throughout. It is useful for thematerial to be thermoplastic so as to allow the formation of the thinwall after the tube has been extruded. It may be formed frompolyvinylchloride, polyurethane, C-Flex (Concept Polymer TechnologiesInc., Clearwater, Fla. 33546) or the like. To reduce the pressuredifference across the thin wall required to close the valve it isadvantageous for the material of tube 53 to be relatively soft with ashore hardness in the range of 40A to 75A. For example, Tygon S-40-HLwith a shore hardness of 40A or Tygon S-62-HL with a shore hardness of55A both made by Norton Co. of Akron Ohio are preferable choices. Asillustrated, tube 53 has a region 53a intermediate its ends with athinner wall than that of the remainder of the tube. The tubing has agradual transition in wall thickness between the two said regions. Therigid walled enclosure 232 surrounds region 53a and seals it aboutregions 53b and 53c of said tubing. Inlet opening 232b and outletopening 232c of housing 232 are snug fit to seal to the outside normaldiameter of tubing member 53 on either side beyond the central region53a. The midportion of housing 232 has an enlarged region 232a, at leastin one aspect of its diameter as shown in FIG. 6, which accommodates theenlarged region 53a of unitary tubing 53 as it collapses to its closedstate, as illustrated in FIG. 3. A duct 232d is joined to or formed athousing 232 and communicates with chamber 234, formed between thehousing 232 and region 53a. Duct 232d is then connected to a pressurecontroller such as the pressure controller illustrated in FIG. 8. Forthe purpose of sealing seals 53b and 53c via radio frequency, heatsealing or adhesive, or solvent, or for other connective purposes it isadvantageous, but not necessary, to form the housing 232 of the samematerial as the unitary tubing 53. Housing 232 may also be designed toserve as mechanical support for the thin section of region 53a toprevent accidental rupture due to over herniation of region 53a whichcould occur when the interluminal pressure is low and the blood pressureis high. Housing 232 may be blow molded for example from a clearmaterial such as polycarbonate, polyvinyl chloride, PETG or the likewith its walls somewhat inelastic but not necessarily rigid. It can alsobe vacuum formed as a clam shell with section 53a of unitary tubing 53placed within both halves and then sealed by joining the halves to formthe closed clam shell. Outlet region 53b can be, but does not have tobe, constricted by 232b of housing 232 as shown, the purpose of which isdescribed below.

During operation of the pressure sensitive valve, pressurized fluid (orfluid mass) is introduced through duct 232d into chamber 234 whereuponthe pressure causes indentation or contraction of the thin walled region53a of said tubing to displace any blood contained therein leading tocontrolled restriction of the blood flow in unitary tubing 53 from thearterial line 57 to venous line 23. This restriction can be complete asillustrated in FIG. 3 or with small bleed channels as illustrated inFIG. 4 by 53d and 53e. To assure full closure of section 53a asillustrated in FIGS. 3, 4 and 6 at lower pressure differences betweencontrolling interluminal pressure and blood pressure, edges 53g and 53fare preformed, for example with heat, to overcome the otherwiserelatively high stresses inherent in the material that resist folding.It should be understood that for valves used to isolate (e.g., valve 571isolating oxygenator 5 in FIG. 1) a complete obstruction to flow, asillustrated in FIG. 2a, and 3, is required and the channels illustratedat 53a in FIGS. 4, and 6 are undesirable.

As long as the fluid pressure in first pressure chamber 234 actingexternally on the thin wall tube 53a is greater than the pressure insidethe tubing, the valve remains closed. If the pressure inside the tubingis greater than the external fluid pressure, the valve opens, as shownby the dashed lines in FIG. 3 which is a transverse sectional view takenalong lines 3-3' in FIG. 2a. If the pressure at the inlet to the valveis higher and the pressure at the outlet is lower than the externalpressure then the valve does open but only partially and serves as aresistor that maintains inlet pressure at a pressure approximately equalto the fluid pressure applied in chamber 234. It should be understoodthat when the valve is used at the outlet of a constant flow pump (e.g.,roller pump), the cross sectional area opened to flow decreases as thethin walled region of the valve collapses. The combination of decreasedarea and constant flow causes blood velocity and the blood pressure inregion 53a to increase and decrease respectively according toBernoulli's equation. The lower blood pressure in region 53a reduces theinterluminal pressure at which the valve will close. If the resistanceat the outlet of said pressure sensitive valve is low, as is the casebetween valve 531 outlet and venous reservoir 3, then the valve willflutter between opened and closed positions, the frequency ofoscillation being higher with low viscosity (dilute blood) and highReynold's number (higher flow rates). This property can be used to alarmthe user to an open valve condition. For example, if the pressuresensitive valve is used as a pressure relief valve between the arterialand venous lines (531) or across the inlet and outlet of an arterialfilter (771), then clinically it would be very useful to have an alarmincorporated into the valve design to alert the user to the dangerouscondition. This can be done with the fluttering that occurs when thevalve opens. For other uses, as for example the pressure sensitive valveacting as a resistor (231), or a continuous recirculating line, it isundesirable to have fluttering because over time it may cause blooddamage. It therefore would be very useful to be able to control thedegree of or eliminate fluttering.

One method of reducing flutter, according to the present invention,consists of placing a resistance between the port of the pressure reliefvalve and the pressure regulator. Said resistance could, for example, bethe roller clamp valve used with IV drip sets to adjust the rate ofintravenous solution administration. Said resistance, in combinationwith a fluid of appropriate viscosity in interluminal space and thepressure regulator can be used to control the rate of volume changebetween the interluminal space and the pressure regulator and thus therate at which the pressure relief valve can open or close. Increasingthe resistance by closing the valve (or by increasing the viscosity ofthe fluid) reduces the flow rate between the interluminal chamber andthe regulator thus providing increased damping that results in decreasedfluttering. The resistance can also be controlled by inserting variouslengths and/or diameters of tubing between the chamber and pressureregulator.

Another method that may reduce fluttering of region 53a illustrated inFIG. 2a, is to increase the diameter of region 53a as illustrated inFIG. 14 so as to decrease the velocity of the blood therethrough andthereby reduce the pressure differences across the wall of region 53athat is due to differences in blood velocity in region 53a and thenormal section of unitary tubing 53. Alternately, an equal or smaller IDin region 53a may increase the chance of flutter, a flow characteristicdesirable for the aforementioned alarm.

Another method that may reduce fluttering is to increase the resistanceat the valve outlet as for example decreasing the ID at the outlet ofthe valve as indicated by 53b in FIG. 2a. The resistance at the pressurerelief valve outlet can also be increased by using soft durometer walltubing to make the valve. For example, if unitary tubing 53 has adurometer of 55A, (e.g., Tygon S-62-HL) the interluminal pressure issufficient to compress the normal tubing wall. At typical operatingconditions, with the controlling pressure being over 300 mmHg and thevalve outlet pressure below 50 mmHg, the transwall pressure differenceconstricts the lumen of tube 53 whereby its cross section geometryresembles that shown in FIG. 4: with two channels that have a relativelyhigher resistance to flow than the naturally open lumen.

Another way to reduce flutter is to increase the wall thickness and orhardness of the thin wall section, 53a in FIG. 2a.

FIG. 2b illustrates the combination of compliance chamber 241 andpressure monitor 233 that can be used to adjust the pressure of firstpressure chamber 234 of valve 231 shown in FIG. 2a. Pressure monitor 233incorporates pressure transducer, digital display of the pressurereadings and an alarm system. It can be, for example, similiar to model9000 made by DLP of Grand Rapids Mich. Compliance chamber 241 isconnected to the pressure monitor via tube 240 and to interluminal space234 via tube 242. Tube 242 ends with Luer fitting 243 that facilitatesits connection to pressure port 232d of valve 531 shown in FIG. 2a.Stopcock 244, interposed for example in tube 242, is used to pressurizethe compliance chamber, pressure relief valve 531, and pressure monitor233 to the desired interluminal pressure.

Pressure monitor 233 with user-settable low and/or high pressure limitsand alarm capabilities could be used in conjunction with the compliancechamber to signal the open state of the valve. This can be in additionto the visual indication provided by flow through the valve, asdiscussed with reference to FIG. 7a-b. If valve 531 opens prematurely,as may occur due to poor connection between the valve and compliancechamber, resulting in loss of pressure, the low pressure alarm inmonitor 233 alerts the user.

The high pressure alarm alerts the user when the valve opens due toexcess pump outlet pressure. This is possible if the volume ofcompliance chamber 241 is small enough to be sensitive to the volumechange that occurs upon valve opening (e.g. 0.5-1.0 ml). For example, ifcompliance chamber 241, connecting tubes 240 and 242, interluminalvolume 234, and the volume of the pressure transducer have a totalvolume of 40 cc and the set pressure is 300 mmHg, then a 0.5 cc decreasein volume in first pressure chamber 234 that occurs when the valveopens, results in a pressure increase of (40)(760+300)=(40-0.5)(760+P).This solves to P=313 mmHg, or an increase in interluminal pressure of 13mmHg. Thus, the user would set the high alarm 13 mmHg above theinterluminal pressure used to close the valve. It should be obvious thatthe smaller the compliance chamber, the greater the change ininterluminal pressure and the lower the volume change that would set offthe alarm. The disadvantage of decreasing the compliance is that theincrease in set pressure due to the valve opening also increases pumpoutlet pressure because of the increased interluminal pressure.

Another advantage of the pressure relief valves described in FIGS. 2c,and 11 through 16 is that they can transmit the intraluminal fluidpressure and thus can be used as devices to measure pressurenoninvasively as described in my allowed applications U.S. Ser. No.07/852,931 filed Mar. 13, 1992 entitled "Pressure Sensitive Valves forthe Extracorporeal Circuit", and U.S. Pat. No. 5,215,540 entitled"Innovative Pumping System for Peristaltic Pumps", and U.S. Pat. No.5,305,982, which contain similar pressure sensors and control systems.It also would be obvious to those skilled in the art that such pressuresensitive valves could be used to control various functional parameterswhich require blood pressure control.

FIG. 4 illustrates housing 232 and thin wall tubing section 53a thereinof valve 531, shown in FIG. 2a, in a state of contraction with oppositewalls flattened out to make contact and form a complete closure exceptfor two bleed channels 53d and 53e formed at the edges of said tubingsection. These channels allow sufficient blood flow through the tubingto hinder clot formation in tube 53 of valve 531 without taking awayfrom its main purpose of causing an obstruction to flow. The flowthrough bleed channel 53d and 53e may be for example 1 to 5% of the pumpflow. The channels may be formed naturally by the elastic properties ofthe material which dictate that the greatest stresses occur along theedges that fold. Or, if necessary, the channels may also be formed byheating the thin walled section and forming the channels withappropriate dies. The low flow provided by the leak can preventstagnation of blood and thus reduce thrombus formation. To furtherreduce the occurrence of thrombus, it is advantageous to increase theblood velocity in tube 53. This can be achieved for example by makingthe diameter of unitary tube 53, shown in FIG. 1, equivalent to thediameter of the arterial cannula thereby limiting the additionalpressure required at the pressure relief valve inlet when full pump flowis directed through it, to that seen under normal pumping conditions. Inthe preferred diameter the branch Y can be smaller to accommodate apressure relief valve with smaller ID tubing. For example, pressurerelief valve made of 1/4" ID unitary tubing placed across a pump with3/8" ID tubing in the raceway. For this set up, a 3/8"×3/8"×1/4" Yconnector would be used. Though two channels are shown, it should beunderstood that a similar function can be served by one or morechannels.

Alternatively, unitary tubing 53 can be formed of a highly elasticmaterial such as silicone rubber, in which section 53a is permanentlyformed in the closed position, for example as illustrated in FIGS. 2a, 3and 4, said section then requiring a predetermined blood pressure abovethe pressure in the interluminal space 234 to open section 53a of thecorresponding pressure relief valve. The additional pressure can befixed during manufacture by adjusting the thickness of section 53a andthe degree of stress put in the material. It should be understood thatwhen valve 531 is made with elastic section 53a, then the wall thicknessof section 53a can be thicker than the normal wall of unitary tubing 53.It also should be understood that the pressure required to open section53a could be sufficiently high whereby housing 232 serves to supportsaid section and first pressure chamber 234 need not be pressurized.

FIG. 5a is a schematic illustrating the combination of a normally closedpressure relief valve, the pump tubing, two 3-way connectors and theirrespective interconnection according to the present invention. Asillustrated, pump tubing 513 is placed in roller pump 4 with its inlet513a connected to 3-way perfusion connector 514 at 514a and its outlet513b connected to 3-way perfusion connector 515 at 515a. Inlet tubesection 44c of valve 441 is connected to port 515b of connector 515 andoutlet port 44b of valve 441 is connected to port 514b of connector 514.Port 514c of connector 514 is connected to inlet tubing 34 and port 515cof connector 515 is connected to outlet tubing 45, said inlet and outlettubing allowing the combination of pump 4, pressure relief valve 441,and pump tubing 513 to be incorporated within to a standardextracorporeal circuit. For example, inlet tube 34 can be connected tothe arterial reservoir of a bubble oxygenator and outlet tube 45 can bethe arterial line used to deliver blood to the patient duringcardiopulmonary bypass. Another example would be for pump 4 to deliverblood cardioplegia with inlet tube 34 connected to the arterialreservoir of an oxygenator and outlet tube 45 connected to the heatexchanger. Similarly, pump 4 could be used in a dialysis circuit, withinlet tube 34 and outlet tube 45 incorporating said combination intosaid dialysis circuit as well known in the art of perfusion. Asexplained in detail for valve 531 in FIGS. 2a, 3 and 4 by adjusting thepressure of first pressure chamber of valve 441 it is possible to varythe blood pressure at which it would open, assuring that overpressurization anywhere in the circuit beyond the pump outlet would beprevented by allowing recirculation between pump outlet and inlet.

The pressure of the first pressure chamber can be adjusted by adding orremoving volume with compressible or incompressible fluid. The use of asterile physiological solution, as for example saline, as theincompressible solution provides a safety feature: should the thin wallsection develop a leak, the blood would not be contaminated nor wouldthe possibility of gas emboli occur.

Pump 4, being a peristaltic pump, requires that its occlusion of tubing513 be set appropriately. Occlusion by said pump of said tubing is setby adjusting the distance between rollers 510a and 510b, which extendradially, to squeeze tube 513 against pump raceway 4a. This can beachieved in the present invention by a dynamic method that gives anaverage occlusion over the entire segment of tubing 513 being used topump blood. The method consists of pressurizing pressure relief valve441 to a preset pressure, turning pump 4 on at a fixed rotation,clamping outlet tube 45, with for example tubing clamp 591 and adjustingthe occlusion of pump 4, using occlusion setter 510e, until therecirculation flow through valve 441 is barely visible. This method, aswill be described in reference to a visual indication with respect toFIG. 7a-b, allows precise and accurate setting of various degrees ofocclusions by simply adjusting the pressure of first pressure chamber ofvalve 441 and/or the pump speed at which flow through valve 441 justappears as shown in stage bb of FIGS. 7a and 7b.

When pump 4 is used to pump blood to a patient it would be useful forthe user to know when over-pressurization occurs and valve 441 opens.This can be accomplished by an alarm or by visual inspection of thevalve and/or its outlet tubing (as will be described hereinafter). Thereduction in flow to the patient that would accompany recirculationthrough valve 441 to the inlet of the pump can also be indicated by areduction in the arterial pressure of the patient or comparing thereading from a flow meter attached to the arterial line between valve441 and the patient to that expected for the pump speed being used.

Another method to determine the degree of recirculation through thevalve is by clamping the tubing incorporating pressure relief valve 441and noting the increase in either the pump outlet pressure or thepatient arterial pressure. An increase that is greater than acceptablewould suggest an unacceptably high recirculation rate.

The set up described in FIG. 5a can also be used to maintain a constantpump outlet pressure rather than constant flow as for example by settingthe pressure of first pressure chamber 534 described in FIG. 2a to thedesired pressure and allowing pump 4 to pump at a flow rate such that,without the pressure relief valve it would generate a pressure abovethat of the set pressure. In this setup, the valve would open allowingrecirculation of excess flow through valve 4 maintaining the pump outletpressure at the desired level.

To avoid air entrapment within the recirculation line between ports 514band 515b, it is advantageous to have sufficient length of tubing toallow valve 441 to be pushed below the horizontal plane of the saidports as illustrated in FIG. 5b. It is also useful to have said portseither point downward or to enable the user to push them downward whenthe circuit and pressure relief valve are primed and debubbled of air.This allows the lighter air to float to the top and be cleared from thepressure relief valve and its associated tubing.

FIG. 5b illustrates a transverse sectional view of one preferredrelative orientation between the flattened portion of pressure reliefvalve and the pressure indicator that maximizes the user's view of thevalve's open state and the elastic sleeve inflated (pressurized) state,as well as providing easier debubbling of said valve. The debubbling isenhanced by placing the valve below connector 514 and 515. This designfeature provides the user with a clear view of any blood channeling asdescribed in FIG. 7a-b below and the inflation state of the elasticballoon described in reference to FIG. 8. Debubbling is a standardoperating procedure in which bubbles in the extracorporeal circuit areremoved to prevent embolization of the patient.

FIG. 5c illustrates another sectional view of the pressure relief valveand pressure regulator combination shown in FIG. 5a, with a preferredpermutation as defined by angle alpha, said angle being between 30° and60° from the horizontal. Angle alpha allows an excellent visual anglebetween the user's eye 501 and said valve open state and said elasticsleeve inflated state.

FIG. 5d is a schematic similar to that shown in FIG. 5a except that thepressure relief valve 441 is shown with a centrifugal pump 510, and theoutlet of valve 44b is connected to the top of a cardiotomy reservoir 8.As with the roller pump, the pressure relief valve prevents excesspressure at the pump outlet. Should outlet pressure exceed desiredlevels, the extracorporeal pressure will exceed the interluminalpressure, thereby opening thin wall section 44a. As the valve opens, itdirects the pump flow associated with the excess pressure to the top ofcardiotomy reservoir 8. If the connection from said valve to saidreservoir is made at the top, as illustrated in FIG. 5b, an overpressurecondition can be easily spotted by observing the flow at the airinterface at the entrance to the blood reservoir 8 as shown forillustration only, by drops 59. Thus, the flow would indicate the degreeof excess pressure in the extracorporeal circuit. If need be, the rateof flow through said valve could be measured by a timed collection ofthe volume accumulating in said reservoir whose outlet has been clampedshut.

FIG. 6 illustrates another preferred embodiment of a pressure reliefvalve similar to that in FIG. 2a with an improved configuration tobetter visualize the open/closed state of thin wall region 53a, asdescribed in reference to FIGS. 5a and 7a-b. This is accomplished byforming housing 632 of rigid transparent material having a flat wallthat is parallel to flattened wall of region 53a. When opposite walls ofregion 53a meet in a closed state they form a clear plane. When bloodflows between these walls, the walls separate, said separation becomingvisible due to lack of clarity and formation of at least one channel,(e.g., red streaks when the liquid is blood). FIG. 6 also illustrates apressure relief valve with a single bleed channel, 53e, the purpose ofwhich is to reduce thrombus formation. Also illustrated is the locationof the pressure port for the pressure indicator/regulator, ideally it iseither perpendicular as shown in FIGS. 2a, 3 and 4, or parallel to theflattened plane of the thin wall section as shown in FIG. 6. The properorientation of the port to the plane of the flat portion 53a depends onwhether the degree of openness of the pressure relief valve is viewed asshown in FIG. 7a, where said perpendicular orientation is preferred, oras shown in FIG. 7b where said parallel orientation is preferred. Saidproper orientation provides the user with a clear view of any bloodchanneling, as described in FIGS. 7a and 7b and the inflation state ofthe elastic balloon, hereinafter described with reference to FIG. 8,especially when the pressure relief valve is positioned as described inFIG. 5c.

FIG. 7a, also shown in a top view as FIG. 7b, illustrates how changes inoptical characteristics in a pressure relief valve, as for example theone illustrated in FIG. 2a, can be used to detect flow through it and/orits state of openness. When opposite walls of thin wall region 53a of apressure relief valve, as for example that shown in FIG. 2a are squeezedclose, they form a thin, clear, (or white, as discussed below) flattenconfiguration as shown by plane 2353p in FIGS. 7a aa and 7b aa. Whenblood just starts to flow between these walls, the walls separate, saidseparation becoming visible due to an increase in thickness of said thinplane as well as due to a color change from clear (or white, asdiscussed below) to red through the entire length of the thin section53a as shown in FIGS. 7a bb and 7b bb. When the valve fully opens, saidseparation becomes more visible due to a further increase in thicknessof said thin plane and increase area of said color change of the thinsection 53a as shown in FIGS. 7a cc and 7b cc. This unique feature canbe used to dynamically set the occlusion of pump tubing 513 placed inroller pump 4 as shown in FIG. 5a. With this method, the occlusion isset by pressurizing pressure relief valve 441 to a preset value,clamping off outlet tube 45 with clamp 591, and adjusting the occlusionof pump 4 using adjuster 510e until, at a fixed rotation of pump 4, flowwithin valve 441 is barely visible, a visual state between FIG. 7a aaand 7a bb. For an under or over occlusive pump, the flow through thepressure relief valve would decrease or increase respectively as thepump occlusion is adjusted appropriately. To increase the opticaldifferences shown in FIG. 7a between aa, bb and cc, it is desirable tohave a white background to accentuate the said color change. This can beaccomplished for example, with a white tape or white coloring placed onthe housing wall opposite that being viewed, as shown for example by 699in FIG. 6 and by 599 in FIG. 5c. The white coloring can also beimpregnated within the material of the housing wall, or incorporated onone side of the external wall of thin wall section 53a as shown by 53fin FIG. 6.

This dynamic method provides precise and accurate setting of variousdegrees of occlusions by simply adjusting the interluminal pressure ofvalve 441 and/or the pump speed at which flow through valve 441 occurs.Unlike the aforementioned static occlusion method, the dynamic methodgives an average occlusion for both rollers over the entire segment oftubing 513 being used to pump the blood. It also gives a directindication of the back flow such that a relationship between the speedof the roller pump and flow can be developed for any pressure differencebetween pump inlet and outlet (dP) and pump occlusion setting. Thus, atgiven occlusion setting, the net forward flow equals the total forwardflow, which is the product of the pump speed and the pump constant, saidconstant being a function of the ID of pump tubing 513 the length ofsaid tubing compressed in the pump 4 raceway, less the back flow. Theback flow, known from the occlusion setting (e.g., a flow equivalent to5 RPM at a dP of 300 mmHg across said pump), can also be calibrated toproduce a set of curves that give flow at any RPM and dP to give netforward flow. This concept was verified with an experiment where a 3/8"ID tubing was set non-occlusively using 5 RPM and dP of 300 mmHg asexplained above and the flow of said tubing was compared to a tubing setocclusively. At a dP of 300 mmHg across the pump the flow of thenonocclusive pump was equal to that of the occlusive pump less a valueequal to a flow of 5 RPM. Thus at 20 RPM the flow of the nonocclusiveset pump was 450 ml/min as compared to 600 ml/min for the occlusivepump. Similarly, at 100 RPM, the flow of the nonocclusive set pump was2850 ml/min as compared to 3000 ml/min for the occlusive pump. Thus, atdP=300 mmHg the user could increase the pump speed by 5 RPM to get thesame flow as expected with the standard occlusive pump.

It is desirable to form the tubing 513 placed in the pump raceway of thepump loop described in FIG. 5a using a pump tubing with at least onelongitudinal portion of its wall thin, the thickness of said thin wallbeing at least 1/9 or less that of the internal diameter of said tubingas described in my allowed application U.S. Ser. No. 08/016,034, andU.S. Pat. No. 5,215,540 entitled "Innovative Pumping System ForPeristaltic Pumps". The thin wall tube provides several clinicaladvantages. For example, as the inlet pressure to the pump is decreased,the tube starts to collapse thereby decreasing pump flow withoutproducing excess negative inlet pressure. It would also be advantageousto extrude the pump tubing from polyurethane, preferably apolyether-polyurethane with a nominal shore hardness between 70A and80A, as described in the aforementioned U.S. Pat. No. 5,215,540. Thismaterial has been shown to have extended pumping life and reducedspallation (the degradation of material by friction). Thus, thecombination of the pressure relief valve placed across a pump tubingmade of thin wall polyurethane forming a pumping loop, as for example,shown in FIG. 5a, can pump blood without producing excess inlet oroutlet pressure for wider range of flow changes.

FIG. 8 illustrates a sectional view of another preferred embodiment of apressure regulator designed for use with a pressure relief valve,consisting of an elastic cylindrical balloon 833 closed at one end withvalve 837 and sealed to connector 832 by compression fitting 838.Connector 832, which can be for example a male Luer fitting, isconfigured to connect directly to port 232d of the pressure relief valveshown in FIG. 2a. Check valve 837 permits pressurization of chamber 834,formed by balloon 833, connector 832, and check valve 837. The pressurein chamber 834 is transmitted through opening 834a to, for example,interluminal chamber 234 in FIG. 2a. The balloon provides a steadypressure over a range of volumes that is greater than the volume changerequired to open and close the pressure relief valve. A cylindricalballoon has at least 4 advantages over a spherical balloon: 1) it haslow manufacturing costs and higher accuracy because it can be formed byextrusion rather than molding or dipping as is the case with a sphericalballoon, 2) it can be made to have an internal diameter that wouldaccept a standard check valve, 3) its inflated state can be easilydetected by a shape and size change rather than only size change for aspherical balloon, and 4) the pressure-volume relationship of acylindrical balloon, determined by its elastic properties and physicaldimensions (see co-pending application U.S. Ser. No. 876,627) can beadjusted by the user by adjusting its length. The pressure required toinflate a cylindrical balloon is a function of its internal diameter.For short balloons with a ratio of ID/length<10, the length also affectsthe inflating pressure. For such balloons an effective diameter canapproximate the diameter to be used in the relationship between diameterand inflating pressure. Since the effective diameter for a shortcylinder can be approximated by (Length×Diameter)/(Length+Diameter),then the inflating pressure for any specific cylindrical balloon can beadjusted by adjusting the length of the balloon that is allowed toexpand. To that end, cylindrical sleeve 838 placed over balloon 833limits the balloon expansion which results in a smaller balloon, asmaller effective diameter and therefore a higher inflating pressure.Sleeve 838 can also provide mechanical support to prevent the elasticcylinder from disconnecting at 833b from connector 832. Sleeve 838 canbe replaced by other sleeves of different lengths, as for examplesleeves 848 or 858, to yield different pressures, each of said sleevescan be marked appropriately, as for example color coded and/ornumerically, to indicate the inflation volume required and/or thepressure it provides. It is also possible to provide different pressurevs. volume characteristics by having the sleeves made of an elasticmaterial, the combination of the balloon and sleeve adapted to givedesired results. Valve 837 can, for example, be a check valve (Model No.810ACS made by Halkey Medical of St. Petersburg, Fla. 33702-1098) whoseopen end accepts the Luer fitting of a syringe and is designed to fill,hold and release controlled amounts of fluids on demand. Alternatively,valve 837 can be replaced with a fitting that accepts a standard 3 portstopcock with one port of the stopcock attached to the elastic sleeve,another port allowing changes in the sleeve volume, and the thirdconnected to a conduit leading to a pressure transducer. Thisarrangement allows precise measurements of the controlling pressures. Itshould be understood by those skilled in the art that it would beadvantageous if all connections required to be made by the user areformed with a standard Luer-lock fitting. It should be understood that apressure regulator like that illustrated in FIG. 8 can be attacheddirectly to the housing of the pressure relief valve as shown in FIGS.5a-d.

FIG. 9 illustrates the relationship between pressure and volume fordifferent lengths of cylindrical elastic sleeves, said relationshipbeing useful for adjusting the control pressure for a pressure reliefvalve. The sleeves were formed of gum rubber material with no fillers orplasticizers, cured by conventional sulfur cure system and incorporatingphenolic anti-oxidants. The data indicates that a pressure range can behad with one sleeve by adjusting the volume and/or the length used forinflating said sleeve. For example, the data shown in FIG. 9 wascollected for sleeves with an internal diameter of 0.25", a wallthickness of 0.025"and cut to lengths of 0.5 (dark squares), 0.75 (whitesquares) and 1.0"(diamond). Regulating pressure between 300 to 450 mmHgdepending on its inflation and initial length can be obtained,indicating that the degree of inflation and/or length can be used toadjust the regulated pressure.

FIG. 10 is a sectional view of another preferred embodiment of apressure regulator with spring 10 mm providing an elastic force. Thespring is housed in, and attached to a sealed, flexible polymericenvelope 1063 forming chamber 1034. The connections are made at 1063awith 1039a and 1039d and at 1063b with 1039b and 1039c. The combinationof the spring for elasticity and the envelope for sealing can provideadjustments for either control of pressure by expanding the spring, orof suction by compressing the spring via the addition or subtraction ofvolume into chamber 1034 respectively. This volume may be altered viacheck valve 1037 sealed in port 1063e. The controlled pressure isconducted through orifice 1034a, an interconnecting tubing (not shown)to, for example, port 232d of valve 531 shown in FIG. 2a and thereby tochamber 234, to impart selected negative or positive pressure uponsection 53a of valve 531. The pressure generated by spring 1033 is verydependent on the degree of compression of the spring and therefore onthe volume within chamber 1034. This can be used to the user's advantageby providing scale 1068 and pointer 1063c, the combination of whichindicate the degree of negative or positive pressure applied on section53a. Pressure scale 1068 can be expressed as a % of maximum negative orpositive pressure possible, in mmHg or alternatively in centimeters ofwater.

The ratio of the volume 1034 of regulator 1030 relative to the volumechange due to section 53a opening or closing can also be used to providea variable pressure regulator. If the said change in volume of 53a islarge compared to volume 1034 then as valve 531 opens, volume 1034 mustincrease thereby expanding spring 1033 and generating greater pressureon thin wall section 53a. If the change in said volume 53a is very smallcompared to the volume 1034 then there will be no significant change in1034 as the valve opens or closes and the pressure applied to 53a wouldbe essentially unchanged. The type of pressure regulation, steady orvariable is determined by the user who can, as described for theaforementioned suction regulator, add another volume between pressurecontroller 1030 and controlled valve 531. It should be obvious thatthere are many other means for pressurizing pressure relief valves. Forexample, a pressure indicating means (e.g., gauge, pressure transducer)with or without a compliance chamber can be used in combination with aninflating means, as for example a syringe, to perform the same functionas described for the elastic sleeve in FIG. 8.

FIG. 11a illustrates a cross sectional view of a pressure relief valveutilizing two Y-connectors, thin wall tubing and an elastic housing.Thin wall tube 1171 with one end affixed to 3-way connector 1176 at1176b and the other end affixed to Y-connector 1175 at 1175b, forms asmooth blood path. End 1175c and end 1175d of said Y-connector 1175 maybe connected to the inlet of pump tubing 513a and inlet tube 34respectively as shown in FIGS. 19 and 5a. End 1176c and end 1176d ofsaid Y-connector 1176 may be connected to outlet tube 45 and to outletof pump tube 513b respectively. The Y-connectors used can be, forexample, standard perfusion tubing connectors supplied by Texas MedicalProducts of Houston Tex. Housing 1172 seals thin wall tube 1171 byforming a tight fit over 1171b onto 1176b at end 1172a and a tight fitover 1171c onto 1176b at end 1172b, as better illustrated in FIG. 11b,to form chamber 1134 whose pressure, positive or negative, can beadjusted as described previously. Thin wall tube 1171 can be made of atransparent thermoplastic, as for example polyurethane or polyvinylchloride, as described previously, and its section 1171a serving as thepressure relief section can be formed as described with respect to FIGS.3, 4 and 6. The advantages of this design are that the valve assemblyrequires no additional connectors, because it makes use of the alreadypresent Y-connectors that are used in the cardiopulmonary bypasscircuit. These Y-connectors, for example as illustrated in FIG. 5a beplaced such that connector 1176 replaces 3-way connector 515, connector1175 replaces 3-way connector 514, and the pressure relief valvedescribed herein replaces valve 441 shown in FIG. 5a, said replacementsproviding the same function as that described with respect to FIGS.5a-d.

FIG. 12 illustrates a cross sectional view of another preferredembodiment of a pressure relief valve. Thin wall tube 1271 has its ends1271b and 1271c affixed and sealed to the inside diameter of thickersupporting sleeves 1275 and 1276 respectively. The outside diameter ofsupporting sleeves 1275 and 1276 are sealed to the inside diameter ateach end of housing 1272 thereby forming interluminal space 1234 thatcan be pressurized as described, for example, with respect to FIG. 2a.Midsection 1271a is processed to form a flat section such that it formsa smooth blood path and allows easy closure of opposite walls, or may beformed as described with respect to FIGS. 3, 4, and 6. The ID of thethin walled tube is made to accept standard perfusion connectors, as forexample 1/4" and 3/8" connectors (Baxter/Bentley Lab, Irvine Calif.)thereby allowing the user to easily incorporate said valve anywhere inthe extracorporeal circuit as shown for example in FIG. 1. Thin walledtube 1271 can for example be made of polyvinyl chloride, polyurethane orother thermoplastic material used to extrude tubing for use in rollerpumps. The sleeves and housing can be made of similar material tosimplify the required seals between the sleeve, thin walled tubing andhousing. The housing provides strength to support the interluminalpressure, and provides sufficient elasticity for the user to be able toinsert said standard perfusion connectors into the thin walledtubing/sleeve/housing combination. The seals can be formed for exampleby solvent bonding or heat.

FIG. 13 illustrates a design utilizing end cap spacers 1335 and 1336serving to secure and seal housing 1332 and unitary tubing 53. Saidparts form enclosed interluminal chamber 1334 between housing ends 1332band 1332c and the ends of the outer diameter of tube 53 at 53b and 53c.An example of the latter is part number 147ACC from Halkey-Roberts (St.Petersburg Fla. 33716) which also has a skirt shown as 1335a and 1336afor spacer 1335 and 1336 respectively. The outlet spacer may have asmaller inside diameter with thicker walls so as to constrict the outletof the blood path, to thereby reduce fluttering as described withrespect to FIG. 2a.

FIG. 14 illustrates a cross section of a pressure relief valve wherebythe diameter of thin section 53a has been increased to form a pressurerelief valve with a wider diameter at least in one aspect of the thinwall section. The diameter should reduce the blood velocity and therebyreduce fluttering as described in reference to FIG. 2a. Also illustratedis an alternate housing embodiment for thin walled region 53a utilizinga clear thermoplastic cylindrical housing sleeve 1432 made, for example,of the same material as unitary tube 53. Sleeve 1432 is heat sealed tounitary tubing 53 at 53b and 53c and to pressure control line 1423 at1423a, said seals hermetically enclosing thin walled section 53a andforming space 1434. This design has the advantage that during assemblyof the device, it is easier to insert tube 53 into large cylindricalhousing 1432 after which the seals are formed rather than through thetight seals shown, for example, in FIG. 2a. This design, which lendsitself to inexpensive mass automated production,is also suited forpressure relief valves made of thin wall tubing as described withreference to FIG. 12.

FIG. 15 illustrates a cross sectional view of another preferredembodiment of a pressure relief valve. Thin wall tube 1571 has its ends1571b and 1571c folded over ends 1572b and 1572c of housing 1572respectively. The folded edges of tube 1571 are affixed and sealed tohousing 1572 by standard tubing 1561 and 1562, said standard tubingpositioned to entrap said thin wall tube against said connectors' ends.It may be advantageous to use protrusions such as barbed fittings on theoutside diameter of housing ends to better secure the connectionsbetween said standard tubing, said thin wall tubing and said housingends. Standard tubing 1561 and 1562 preferably consists of a length ofpolymeric material such as polyvinylchloride, polyurethane, C-flex orthe like. Housing 1572 can for example be like a standard perfusionconnector with Luer-fitting shown as 1572d (Baxter/Bentley Lab IrvineCalif.), with an ID sufficiently large to accommodate said thin walltubing in a closed state, as explained in reference to FIG. 3. The sealsmade by edges 1571b and 1571c with affixed tubing 1561 and 1562 andedges 1572b and 1572c form a sealed interluminal space 1534 between theouter diameter of tubing 1571 and the inner surface of connector 1572.Connector 1572 as a standard connector comes with female Luer fitting1572d which provides communication for interluminal space 1534 and, forexample, pressure regulator referred to in FIG. 8. Mid-section 1571a isprocessed to form a flat section such that it forms a smooth blood pathand allows easy closure of opposite walls with the noted exceptions asdescribed with respect to FIGS. 3, 4 and 6. The OD of thin walled tubeis made so that when collapsed its half perimeter is slightly smallerthan the ID of connector 1572. This allows equal communication of space1534 within said valve. Standard connector 1572 allows the user toeasily incorporate said valve anywhere in the extracorporeal circuit asshown for example in FIG. 1 by using standard tubing for 1561 and 1562.Thin walled tube 1571 can, for example, be made of polyvinyl chloride,polyurethane or other thermoplastic material used to extrude tubing foruse in roller pumps.

FIG. 16a illustrates a cross sectional view of a pressure relief valveconstructed with 3 layers of thermoplastic membranes such as polyvinylchloride, polyurethane or other blood compatible material that bondsecurely by methods such as solvent bonding, heat, radio frequencywelding or the like. As depicted, layer 1672 is sealed to thin wallmembrane 1671 forming first pressure chamber 1634, and layer 1673 andthin wall membrane 1671 forms a blood path 1674 that providescommunication between inlet tube 1612 and outlet tube 1613. At theinlet, tube 1612 and membrane 1671 are sealed along their perimeterbetween layer 1672 and 1673 sealed at 1612b, 1671b, 1672b and 1673brespectively. At the outlet, tube 1612 and membrane 1671 are sealedalong their perimeter at 1612c, 1671c, 1672c and 1673c respectively.Port 1672d formed within layer 1672 provides communication between firstpressure chamber 1634 and a pressure transducer means similar to thatfor the pressure relief valve described in FIG. 2a. Port 1672d can beformed as part of layer 1672 as shown in FIG. 16a, or attached to saidlayer by aforementioned standard means. Alternatively, the communicationport 1672d can be formed along the sealing perimeter so it is orientedparallel to thin layer 1671 as shown in

FIGS. 16b and 16c, thus providing the advantage of such an orientationas described in reference to FIG. 6. Though the 3 layer design resultsin a valve with physical discontinuities along the seal between the thinand thick wall layers, these areas of stagnation are not prohibitive forshort term use such as cardiopulmonary bypass. The advantage of the3-layer design is that it is very adaptable to mass production. Itshould be understood that as explained with respect to FIGS. 5a, 7a, and7b it is of great clinical advantage to have at layers 1671 and 1672transparent to allow a clear view of the open state of said valve andlayer 1673 opaque white.

FIG. 17a illustrates a cross sectional view of a pressure relief valvecomposed of a unitary tube 53 having thin wall section 53a that ismaintained closed by an elastic loaded clamp 1780. As shown, in FIG.17b, which is a sectional view along line 17-17' of the pressure reliefvalve shown in FIG. 17a, thin wall section 53a is squeezed shut betweensection 1780a and 1780b of clamp 1780. The force of closure is providedby the resiliency of ring 1780c of clamp 1780 and/or by elastic band1733. The force of closure must be equal to or greater than the forcerequired to overcome the elasticity of section 53a plus the separatingforce due to any pressure difference across the thin wall section 53a.When the pressure within tube 53 increases to generate a force greaterthan said elastic force, section 53a opens, opening pressure reliefvalve in a similar manner as explained with respect to FIGS. 2a, 3 and4. The pressure at which the valve opens can be adjusted by the physicalparameters of band 1733 or ring 1780c. For example, increasing thewidth, decreasing the diameter or increasing the thickness of band 1733or ring 1780c would increase the pressure at which the valve would open.

FIG. 18a illustrates a cross sectional view of a pressure relief valvewith pressure regulation provided with another form of a clamp similarto the clamp described in FIGS. 17a and 17b. Here, the thin wall section53a is sandwiched between two members, 1880 and 1881, each of saidmembers having a flat surface 1880a and 1881a respectively said flatsurface contacting thin wall section 53a as shown in FIGS. 18a and 18b,the latter being a sectional view along line 18-18' of the pressurerelief valve shown in FIG. 18a. Members 1880 and 1881 are forced towardseach other to squeeze section 53a closed by the force of elastic band1833. Assuming that the walls of section 53a are free to move, thepressure relief valve opens when the pressure within tube 53a issufficient to overcome the force of elastic band 1833.

FIG. 19 illustrates a cross sectional view of a pressure relief valvesimilar to that shown in FIGS. 17a and 17b except that the closing forceprovided by the elastic band has been replaced by an adjustable springforce. As shown, thin wall section 53a is squeezed shut between section1980a and 1980b of clamp 1980. The force of closure is provided byspring 1933, said spring being supported at one end by rotational member1982 and at its other end by slot 1980c in clamp portion 1980a. Theclosure force provided by the spring can be adjusted by rotationalmember 1982, said member having head 1982a used for rotation at one endand a thread at its other end 1982b, said threaded end engaging matingthread 1980c in clamping portion 1980. By rotating member 1982, spring1933 can be squeezed or released thereby providing an adjustable force.Appropriate selection of spring 1933 allows various permutations ofcontrols. For example, using a long spring with a low spring constant(Force=Spring constant*Compressed distance) would require greatercompression than a short spring with a larger spring constant. Thelonger spring would result in a fairly constant opening force becausethe distance required to open the valve (separate walls of section 53a)is insignificant compared to the overall distance the spring iscompressed. Similarly, the shorter spring would require an increasedopening force because the distance required to open the valve issignificant compared to the overall distance the spring is compressed.It should be obvious to those skilled in the art that other permutationsof spring length, spring force, spring shape or the shape of the springwire can easily be designed. It should also be obvious that washersand/or spacers can be placed between advancing and rotational parts, asfor example between said spring 1933 and said rotational member 1982.

FIGS. 20a and 20b illustrate a cross sectional view of another pressurerelief valve similar to that shown in FIG. 19 also utilizing anadjustable spring force to close thin wall section 53a with the springforce directly over said section 53a. As shown, section 53a is placedand is supported within C frame 2080. Section 53a is squeezed on one ofits sides by the lower section 2080a of said C frame and on its otherside by upper clamping means 2081. Rotating member 2082 engages one sideof spring 2033 forcing it against said upper clamping means 2081. Themagnitude of said force depends on the characteristics of the spring andthe degree of spring compression, said compression being adjustable byrotating member 2082 thereby moving said member in relation to said Cframe by way of thread 2080c that mates a corresponding thread 2082c ofrotating member 2082. Functionally, the spring replaces the pressurewithin first pressure chamber described for pressure relief valve inFIG. 2a, where higher compression requires increased blood pressure toopen thin wall section 53a.

The arrangement shown in FIGS. 20a and 20b could also be used to controlnegative pressure as described with respect to FIG. 22. For suctioncontrol, spring 2033 would be affixed to rotating member at 2082c and toupper clamping means at 2081b. In addition, the outer walls of section53a that are parallel to, and are squeezed by upper clamping means 2081at 2081a and section 2080a of said C frame, would be attached alongtheir plane of contact to said section of C frame and upper clampingmeans. By anchoring said thin section to the clamp 2080 and C-clampmeans 2081 by adhesive or heat seal, and by having rotational means 2082expand spring 2033, section 53a would be normally open, closing when theblood pressure drops below atmospheric pressure to a level sufficient toovercome the resilience of spring 2033 that otherwise maintains saidsection open. The negative pressure at which the valve closes can beadjusted by said rotational means expanding said spring by movingfurther away from said section 2080a of said C-frame. To assurevisualization of the open/close state of the valve as explained withregards to FIG. 7a, it is desirable to have at least one side of theC-clamp transparent.

The thin wall section being compressed closed as shown in FIGS. 17-20,can be thicker if a softer material is used (e.g. Shore 40A). Suchchange however can result in decreased accuracy and increasedhysteresis.

FIG. 21a illustrates a pressure relief valve utilizing the combinationof a tube, extruded with a thin wall separating two sides of said tube,and perfusion connectors for the valve assembly and blood flow. Tube2191 with one end affixed to perfusion connector 1176 and the other endaffixed to perfusion connector 1175 forms a smooth blood path 2174. Thinwall section 2191A is extruded as part of tubing 2191 as illustrated ina cross sectional view along line 21b-21b' and shown in FIG. 21b.Perfusion connectors 1176 and 1175 seal section 2191A to the insidediameter of tube 2191 at sections 2191B and 2191C respectively, creatinginterluminal space 2134. Interluminal space 2134 may have positivenegative pressure which may be adjusted and regulated as describedpreviously. Port 2195 must be affixed to tube 2191 at section 2191d inorder to allow connection to a pressure regulating device describedpreviously. The advantages of this design are that the valve is extrudedas a single piece of tubing, and the valve assembly makes use of thealready present perfusion connectors that are used in thecardiopulmonary bypass circuit. These perfusion connectors can forexample be placed such that connector 1176 can replace 3-way connector515, connector 1175 can replace 3-way connector 514, and the pressurerelief valve described herein can replace valve 441 shown in FIG. 5a,said replacements providing the same function as that described withrespect to FIG. 5a. The arch or length of thin wall 2191A may be alteredby altering the perimeter of the external curvature to provide a valvewith a complete or partial closure. The thickness of thin wall 2191a maybe adjusted to force the formation of one or two bleed channels at thepoint the thin wall joins the tube wall. Providing a thicker walladjacent the tube wall will create a bleed channel adjacent the thickwall. Bleed channel 2191g may also be extruded into the thick wallsection 2191 at the time the section is extruded. Shortening the overalllength of thin wall 2191a will enable partial closure for modulating,but not stopping, flow through this valve configuration.

FIG. 21c illustrates a cross sectional view of another embodiment for apressure relief valve as shown in FIG. 21b except that a coextruded tubewith a thin wall inside layer separating the blood and pressureregulating is utilized. As shown, tube 2191 with a heavier wall iscoextruded with a thin wall tube 2193, after which the two layers arepeeled apart to form first pressure chamber 2134 similar to that shownin FIG. 21a as coextruded inside said tube. Tube 2193 is sealed to tube2191 from section 2191e to 2191f. Either of the embodiments illustratedin FIG. 21b and FIG. 21c may be further altered in a post extrusionprocedure, to alter the configuration of the thin wall. For example, theresistance of wall 2191a to completely close can be significantlyreduced post extrusion by forcing a heated rod through the extrudedsection, or by flattening the entire assembly at the mid sectionthereof.

FIG. 22 shows pressure relief valve 281 placed at the inlet to rollerpump 9. As illustrated, the pump used for suction and the pressurerelief valve is used to limit the negative pressure applied to the bloodat the inlet to said valve. It also provides easy to set occlusion ofthe pump. Thus, the pressure within first chamber is set by, forexample, aforementioned negative pressure regulator 1030 described inFIG. 10, such that pressure relief valve, for example as described inFIG. 2a, is normally open as long as the blood pressure at the outlet ofvalve 281 remains above pressure in said first chamber. To set theocclusion of pump 9, the pressure in first pressure chamber 2234 is setto a desired negative level (e.g., -50 mmHg), the inlet to valve 281 isclamped off, the pump is set to a desirable speed (e.g., 50 RPM) and theocclusion of pump 9 is adjusted with adjuster 51Oc until flow throughthe valve just occurs as described in reference to FIGS. 7a and 7b. Atthe appropriate occlusion, the forward flow provided by the pump isequal to the back flow through nonocclusive section 2228. It should benoted that the negative pressure can also be set in a less accurate wayby removing a known volume from chamber 2234 thereby reducing itspressure and maintaining the valve open until the blood pressure exceedsthe negative pressure required to close said valve. As section 28acollapses, the negative pressure in chamber 2234 changes as a functionof the ratio of the volume in chamber 2234 to the volume change causedby said collapse as explained with respect to FIG. 10. It is noted thatwhen a pressure relief valve is created for suction control, the housingshould be sufficiently rigid to withstand any deformation that couldaffect said negative pressure.

It is desirable to form the tubing 28 placed in the pump raceway of thepump loop described in FIG. 22 using a pump tubing with at least onelongitudinal portion of its wall thin, the thickness of said thin wallbeing at least 1/9 or less than that of the internal diameter of saidtubing as described in my aforementioned U.S. Pat. No. 5,215,540;entitled "Innovative Pumping System For Peristaltic Pumps". The thinwall tube provides several clinical advantages. For example, as theinlet pressure to the pump is decreased, the tube starts to collapsethereby decreasing pump flow without producing excess negative inletpressure. It would also be advantageous to extrude the pump tubing frompolyurethane, preferably a polyether-polyurethane with a nominal shorehardness below 80A. This material has been shown to have extendedpumping life and reduced spallation (the degradation of material byfriction). Thus, a polyurethane tubing having a longitudinal thin walland another section, at its inlet, with a thinner wall forming apressure relief sensitive valve, as for example, shown in FIG. 22, canpump blood without producing excess inlet, isolate the patient fromexcess suction and enable noninvasive pressure measurements.

Other examples of typical uses for the novel pressure sensitive devicesare illustrated in FIGS. 23 and 24. FIG. 23 illustrate a unitary pumptubing 2353 incorporating a first thin wall section 2353a serving as aninline reservoir at the inlet to pump 4, a pumping section 2353b placedin the pump, and a second thin wall section 2353c serving as an inlinepressure isolator. The first and second thin wall sections are shownsealed within housing 2332a and 2332, respectively forming interluminalchambers 2334a, and 2334. Chamber 2334a may be pressurized viainterconnected tubing 2333a, said pressurization determining the bloodpressure at which reservoir 2353a collapses or expands within housing2334a. Section 2353a can for example have a diameter that is 2 to 10times that of tube 2353 and its wall correspondingly thinner. Becausewall 2353a is relatively thin, the blood pressure is transmitted acrossit to chamber 2334a and then via tube 2333a to pressure sensor 2342awithin electromechanical unit 2342 where it is compared to a pressureset by the user. Should the pressure decrease below acceptable values,unit 2342 would either slow down or stop pump 4. Enlarged section 2353aprovides compliance between the pump inlet and the patient, saidcompliance smoothing the operation of the pump and its control mechanismduring inconsistent inlet flow. The degree of compliance is determinedby the ratio of air volume in said first pressure chamber volume to thevolume change caused by a pressure differential which is reflected inthe motion of wall 2353a. The ability to control the pressure at whichsaid enlarged section starts to collapse, allows, for example, its useas a replacement for the aforementioned passive bladder operating bygravity currently placed at the pump inlet during ECMO cases. To avoidgravitational collection of red cells and reduce stagnation, it isadvantageous to place the reservoir formed by section 2353a vertically,thereby allowing gravity to act parallel to the flow.

At the pump outlet, inline pressure measurements without largecompliance are usually sufficient. Thus, thin section 2353c may have thesame wall thickness as section 2353a but with a diameter equivalent totube 2353. Because wall 2353 is relatively thin, the blood pressure istransmitted across it to chamber 2334 and then via tube 2333 to pressuresensor 2343b within electromechanical unit 2342 where it is compared toa pressure set by the user. Due to smaller volume changes allowed bysection 2353c, it may be useful to fill space 2334 with a liquid toprovide reduced compliance between section 2353c and transducer 2342b.Should the pressure increase above acceptable values, unit 2342 wouldeither slow down or stop the pump. It should be obvious that transducers2342a and 2342b may be of a variety of types, as for example a solidstate pressure transducer, an electromechanical pressure switch (e.g.,Model #MPL 533 of MPL Fort Lauderdale, Fla. U.S.A.), or other mechanismsthat respond to changes in pressure or volume. In general, a largediameter section, as 2353a, would be used for mechanisms that requirelarge volume changes, and smaller diameters sections, as 2353c, would beuseful for mechanisms requiring low volume changes. Thus, the type ofcontrol mechanism used at inlet or outlet of pump 4 would dictate thediameter of the thin wall to be used. Again, it would be of clinicaladvantage to form the two pressure sensitive sections and pumpingsection from a polyurethane tube having its ID at least 9 times largerthan its wall thickness.

FIG. 24 illustrates another simple but very accurate pressure or vacuumregulator for a closed system as a pressure relief valve. This regulatoris composed of two essentially identical pressure isolators 2400 and2410 interconnected via flexible tube 2406 and three way stopcock 2405.Pressure isolator 2400 is composed of rigid, generally cylindrical,transparent, housing 2401. Housing 2401 encompasses two variable volumechambers 2402 and 2404 with a common wall made of diaphragm 2403circumstantially sealed midway in housing 2401. The position of thediaphragm determines the relative volume of chambers 2402 and 2404. Thevolume of either chamber 2402 or 2404 can be anywhere from almost 0 toalmost the volume formed by housing 2401, and can be expressed asfollows: volume 2402+volume 2404=the volume formed by housing 2401 lessthe volume of diaphragm 2403. Diaphragm 2403 can move freely withinconsequential elastic stress or force, until it is supported by thewalls of housing 2401. Pressure isolator 2410 is similar in constructionand function to pressure isolator 2410. It too is composed of rigid,generally cylindrical, housing 2411 forming a chamber that is dividedinto two variable volume chambers 2412 and 2414 with a common wall madeof loose diaphragm 2413 circumstantially sealed midway in housing 2411.Pressure isolators 2400 and 2410 can be similar in construction to thePressure Monitor Separator (Cat. No. PMS-2) made by Delta MedicalIndustries Costa Mesa, Calif. 92626, U.S.A.

To form a pressure regulator, chamber 2402 of pressure isolator 2400 isconnected to chamber 2412 of pressure isolator 2410 via tube 2406, theconnections made at port 2401a and 2411a respectively. The entire volumeof chambers 2402 and 2412, the interconnecting tubing and stopcock 2405is filled with liquid 2408. During said filling it is advantageous, butnot essential, to having diaphragms 2403 and 2413 at their midposition(e.g., volume 2402=volume 2404 and volume 2412=volume 2414). The fillingmay be made with 3-way stopcock 2405 interposed between tubing and saidchambers with the connections made, for example, via standard Luer-lockconnectors. Thus, chambers 2402 and 2412 are interconnected and filledwith a liquid, the liquid being able to flow freely therebetween. Thedirection of flow depends on the pressure difference between diaphragms2403 and 2413, this difference equals the hydraulic height plus thepressure difference between chambers 2404 and 2414. Pressure regulationis achieved by having chamber 2404 of pressure isolator 2400 connected,for example, to interluminal volume 574 of pressure sensitive valve 571via stopcock 2415, tube 2407, and fitting 2407a engaging port 572d. Itcan be advantageous to have said connections made via standard Luer-lockfittings, tight slip-on connection, or through permanent connectionsthat would reduce the chances of fluid 2408 leaking. Pressure isolator2410 is elevated above pressure isolator 2400 to a height that will givea hydraulic pressure equal to the control pressure desired for pressurerelief valve 571. For example, this can be done by moving clamp 2452vertically with respect to clamp 2453, along support rod 2450, saidclamps supporting pressure isolators 2410 and 2400 respectively. Lockingmechanisms 2452b and 2453b can be opened to slide clamps 2452 and 2453respectively, and closed at the desired height. To facilitatedetermination of height differences between pressure isolator 2410 and2400 scale 2451 can be incorporated into rod 2450. Using stopcock 2415and a syringe, the sealed volume formed by the chambers 574 and 2404 andtube 2418 is pressurized with a fluid, for example air, until diaphragm2413 is above its midpoint. This assures that the diaphragm can movefreely without being impeded by housing 2401 and pressure is controlledover the expected changes in volume 574 due to the valve opening andclosing. Negative pressure can be controlled by either lowering pressureisolator 2410 below pressure isolator 2400, or by engaging port 572d ofvalve 571 with tube 2417 instead of tube 2407. The aforementionedregulation requires that the volume change due to movement of saiddiaphragm be greater than the volume change in chamber 574 required inregion 57a to open and close device 571. In addition, the volume changein 2404 and 2402 should not cause a significant change in overallhydraulic pressure. This can be achieved by enlarging the crosssectional area of chambers 2402 and 2404 to provide said chamber with avolume that is significantly above the volume change required to affectthe opening/closing of controlled pressure valve. To further minimizethe changes in regulated pressure due to diaphragm motion, it isadvantageous to make isolators 2400 and 2410 identical in all respectsand provide a linear change in volume due to a vertical motion of thediaphragms. This design would allow liquid 2408 moving vertically tocause a change in volume of chambers 2402 and 2412 without changing thecontrolled pressure. For example, a decrease in volume of chamber 2412is accompanied by a drop in the liquid level relative to scale 2451.However, the decrease in volume of chamber 2402 is also accompanied byan increase in volume 2412 of chamber 2412 which in turn is accompaniedby a drop in its liquid along scale 2451 said drop equals theaforementioned drop in chamber 2400. Since the two levels move equalvertical distance, there is no net change in the pressure liquid 2408generates. It should be pointed out that tubes 2406 and 2407 allowpressure isolator 2400 to be placed at a variety of heights relative tovalve 571 providing large possible changes of positive or negativepressure control. Liquid 2408 is chosen according to the pressure orvacuum desired, using liquids with low density (e.g., saline) for lowpressure and liquids with high density (e.g., mercury) for highpressure. The limiting factor being accuracy, the greater the heightdifference between ports 2411a and 2401a as compared to the liquidlevels in chambers 2402 and 2412 the greater the accuracy. The accuracycan also be increased by using a flexible but inelastic tube 2406 so asto prevent any changes in the liquid level due to tube 2406 herniating.If high density (e.g., mercury) is used for liquid 2408 then, ifdesired, it is possible to change the fluid in chambers 2404, 574 andtubing 2407 from gas to low density liquid (e.g., saline) withoutcausing a significant error in controlled pressure. The regulatedpressure set initially is also maintained by rod 2450 and locking clamps2452 and 2453 that fix the distance between pressure isolators 2400 and2410.

By utilizing liquid in tubing 2407, pressure regulator 2410 can also beused to facilitate control over fluttering of pressure relief valvebeing controlled, as described before. Valve fluttering can also becontrolled by placing adjustable valve 2409 in tube 2406 or properlychoosing the internal diameter of tube 2406. Port 2411b can be eitherconnected to a pressure or vacuum source or be left open to atmosphere.Housings 2401 and 2411 can be made of rigid thermoplastic such aspolyvinyl chloride and diaphragm 2403 can be a rolling diaphragm thatprovides inconsequential resistance to movement of said diaphragm.

The static pressure regulator can be used for many applications and isnot necessarily limited to the medical field. It could be used to applyand control pressure directly or to interpose an adjustable pressurebetween two points as illustrated will be with respect to the membraneoxygenator.

FIG. 24 also illustrates one of the many applications for the pressureregulator in combination with pressure relief valve. Here, thecombination is used to assure that the pressure on the blood side of amicroporous oxygenator is always greater than the pressure on the gasside of the oxygenator. For this purpose pressure relief valve 571,shown in FIG. 1 and similar to valve 531, is inserted at the outlet ofmembrane oxygenator 5 in tube 57. Chamber 2404 of pressure isolator 2400is connected to chamber 574 via port 572d of valve 571. Pressureisolator 2410 is raised above pressure isolator 2400 to impartsufficient pressure on region 57a of valve 571 to insure its closure.Tube 2417 interconnects chamber 2414 of isolator 2410 via a port 355a totube 355 the latter supplying gas to oxygenator 5. This interconnectionassures that the pressure in chamber 2414 is equal to the inlet gaspressure, said gas pressure being transmitted through diaphragm 2413,liquid 2408, diaphragm 2403, and fluid 2418 to chamber 574 and appliedto thin walled section 57a of valve 571. Thus, the pressure applied onsection 57a is equal to the inlet gas pressure at 2417b plus thehydraulic pressure generated and regulated at chamber 2400. Valve 571remains closed unless the blood pressure in tube 57 overcomes thecombined aforementioned pressures. Should the gas pressure at the inletto the oxygenator increase, the valve will close until the backed upblood flow builds the additional pressure in tube 57 to overcome theadditional pressure on the gas side.

FIG. 25 illustrates how two independent inline pressure isolation valvessimilar to that shown in FIG. 24, separated by tubing section 2535c witha known resistance to flow, can be used to determine flow. The pressurein thin wall section 2535a is transmitted via tube 2533a to pressuremonitor 2542. Similarly, the pressure in thin wall section 2535b is alsotransmitted via tube 2533b to pressure monitor 2542. Pressure monitor2542 may display each of the aforementioned pressures as well as theirarithmetic difference. Using the calculated pressure drop and the knownresistance to flow in section 2535c, the flow can be calculated, fromempirically derived calibration curves, and displayed directly bypressure monitor 2542, thereby serving as a flow meter. It should alsobe obvious that other designs of inline pressure isolators, as forexample that shown in FIG. 21a, could replace pressure isolators shownin FIG. 25. It should also be obvious that the accuracy of this systemis best with liquids having constant viscosity (e.g. constanttemperature, and hematocrit).

FIG. 26 illustrates a sectional view of another preferred embodiment ofa regulator 2030 designed for use with a pressure relief valve that willgenerate negative pressure. Regulator 2630 includes an elasticcylindrical balloon 2633 closed at one end with check valve 2637 andsealed to connector 2632 by a compression fitting. Connector 2632, whichcan be for example a male Luer fitting, is configured to connectdirectly to port 2332d of the pressure relief valve shown in FIG. 22.Check valve 2637 permits evacuation of and maintenance of generatednegative pressure within chamber 2634, said chamber formed by sleeve2633, connector 2632, and check valve 2637. The pressure in chamber 2634is transmitted through opening 2634a to, for example, interluminalchamber 2234 in FIG. 22. A typical relationship between the volume andinternal pressure of a regulator made from a 6.2" long silastic tube5/8" ID, and 1/8" wall is shown in FIG. 27. As can be seen, the negativepressure generated by said sleeve provides either a variable or constantpressure curve depending where along the curve one chooses to operate.When operating in the mid range, a fairly constant pressure is obtainedindependent of the volume. For this range, the collapsed state of thesleeve, as indicated by the dashed lines in FIG. 26, can be used toindicate that negative pressure is being applied to chamber 2234 ofvalve 281. It should be obvious that different curves can be generateddepending on the material and the length and ratio of ID to wallthickness, as explained with respect to FIG. 8. It should also beunderstood by those skilled in the art that it would be advantageous ifall connections required to be made by the user are formed with astandard Luer-lock fitting. It should also be understood that negativepressure regular 2630 can be attached directly to the port of pressurerelief valve 281 shown in FIG. 22, said regulator replacing shownregulator 1030.

What is claimed:
 1. A system for dynamically setting pump occlusion foran extracorporeal roller pump nonocclusively, said system comprising:(a)a roller pump having at least two rollers for sequentially occluding afirst tubing member to pump an extracorporeal fluid there through, saidfirst tubing member having a pump inlet and a pump outlet; (b) a firstmeans on said roller pump for setting pump occlusion; (c) a secondtubing member for fluid interconnection of said pump outlet and saidpump inlet; (d) a pressure relief valve for closing said second tubingmember below a predetermined pressure; (e) a second means for indicatingfluid flow from said pump outlet to said pump inlet; (f) a third meansfor clamping the pump outlet distal to said second tubing member;wherebya desired occlusion may be obtained by clamping the pump outlet withsaid third means, and adjusting the setting of said first means togenerate a pump pressure equal to said predetermined pressure.
 2. Asystem for dynamically setting pump occlusion for an extra corporealroller pump nonocclusively as claimed in claim 1 wherein said pressurerelief valve and said second means for indicating fluid flow arecombined in a single device, said device comprising:(a) a length oftubing having at least one thin walled portion, said tubing forming atleast part of said second tubing member; (b) an isolating chambersurrounding said thin walled portion said chamber having a monitoringport defined therein; (c) a pressure regulating means connected to saidmonitoring port;whereby said pressure regulating means maintains saidchamber at a pressure sufficient to compress and maintain said thinsection normally closed, and open to excess pressure within saidextracorporeal circuit.
 3. A dynamic method for setting pump occlusionfor an extracorporeal roller pump nonocclusively, said methodcomprising:(a) sequentially occluding a first tubing member with aroller pump to pump an extracorporeal fluid there through, said firsttubing member having a pump inlet and a pump outlet; (b) interconnectingthe said pump outlet and said pump inlet with a second tubing member;(c) closing said second tubing member below a predetermined pressurewith a pressure relief valve; (d) monitoring fluid flow from said pumpoutlet to said pump inlet; (e) clamping the first tubing member distalto said pump outlet; (f) adjusting pump occlusion of said first tubingmember by adjusting an occlusion setting of said roller pump after saidclamping step;whereby a desired occlusion may be obtained by adjustingthe pump occlusion setting to generate a pump pressure equal to or lessthan said predetermined pressure.
 4. A dynamic method for setting pumpocclusion for an extracorporeal roller pump nonocclusively as claimed inclaim 3 whereby said occlusion setting is used to calculate a netextracorporeal flow through said pump.
 5. A dynamic method for settingnon-occlusive pump occlusion for an extracorporeal roller pump asclaimed in claim 3, whereby said adjusting step is accomplished bydisplaying the dynamic occlusion setting, as a function of said pumpspeed and said predetermined pressure on a monitor.
 6. A dynamic methodfor setting nonocclusively pump occlusion for an extracorporeal rollerpump as claimed in claim 5, wherein said dynamic occlusion setting, saidpump speed, and the pump outlet pressure are factored into a logicsequence, the result of which is displayed on said monitor to provide anindication of net pump flow.
 7. A dynamic method for setting theocclusion of an extracorporeal roller pump nonocclusively having a firsttubing member, said first tubing member having a pump inlet and a pumpoutlet, said method comprising:(a) at least partially occluding saidfirst tubing member with a roller pump at a first predetermined pumpspeed to pump an extracorporeal fluid therethrough and thereby generatea pump inlet and a pump outlet pressure, said pump outlet pressure beinga function of said at least partial occlusion and said firstpredetermined pump speed; (b) monitoring the pump outlet pressure at afirst predetermined point; (c) clamping the pump outlet distal to saidpredetermined point; (d) adjusting the pump occlusion of said tubingmember to generate a desired predetermined pump outlet pressure at saidpredetermined pump speed.
 8. A dynamic method for setting pump occlusionfor an extracorporeal roller pump as claimed in claim 7, wherein saidmethod further comprises the step of adjusting the pump speed togenerate said predetermined pump outlet pressure.
 9. A dynamic methodfor setting pump occlusion for an extracorporeal roller pump as claimedin claim 7, wherein said occlusion setting at said predetermined pumpspeed and pump outlet pressure is used to calculate net flow of saidpump.
 10. A dynamic method for setting pump occlusion for anextracorporeal roller pump as claimed in claim 7, wherein said methodfurther comprises limiting the pump outlet pressure at said pump outletto a first predetermined safety level.
 11. A dynamic method for settingpump occlusion for an extracorporeal roller pump as claimed in claim 7,wherein said method further comprises the step of connecting said pumpinlet and said pump outlet with a second tubing member and monitoringpump outlet pressure in said second tubing member.
 12. A dynamic methodfor setting pump occlusion for an extracorporeal roller pump as claimedin claim 11, wherein said method further comprises the step of limitingsaid pump outlet pressure of said second tubing member below apredetermined pressure with a pressure relief valve.
 13. A dynamicmethod for setting pump occlusion for an extracorporeal roller pump asclaimed in claim 7, wherein said pressure monitoring step includes thesteps of determining a first torque required to overcome the elasticforce of said first tubing member and then measuring a second torquerequired to generate said pump outlet pressure and then determining thepump outlet pressure from a function of the difference between thesecond torque and the first torque.
 14. A dynamic method for settingpump occlusion for an extracorporeal roller pump as claimed in claim 13,wherein the pump outlet pressure at said pump outlet is limited to afirst predetermined safety level by limiting the second torque.
 15. Adynamic method for setting a predetermined pump outlet pressure atnon-occlusive settings of pump occlusion in an extracorporeal rollerpump, said pump having a means for adjusting pump occlusion and a firsttubing segment said first tubing segment having a pump inlet and a pumpoutlet, said method comprising:(a) at least partially occluding saidfirst tubing segment with a roller pump at a first predetermined pumpspeed and occlusion setting to pump an extracorporeal fluid therethroughand thereby generate a pump inlet and a pump outlet pressure, said pumpoutlet pressure being a function of said at least partial occlusion andsaid first predetermined pump speed; (b) monitoring the pump outletpressure at a first predetermined point; (c) clamping the pump outletdistal to said predetermined point; (d) adjusting the pump speed at anon-occlusive setting to generate a desired predetermined pump outletpressure;whereby the average occlusion setting over the entire segmentof the first tubing segment of said roller pump can be determined fromsaid first predetermined pump outlet pressure and said firstpredetermined pump speed.
 16. A dynamic method for setting pumpocclusion for an extracorporeal roller pump as claimed in claim 15,wherein said method further comprises the step of adjusting the pumpocclusion to generate said predetermined pump outlet pressure.
 17. Adynamic method for setting pump occlusion for an extracorporeal rollerpump as claimed in claim 15, wherein said occlusion setting at saidpredetermined pump speed and pump outlet pressure is used to calculatenet flow of said pump.
 18. A dynamic method for setting pump occlusionfor an extracorporeal roller pump as claimed in claim 15, wherein saidmethod further comprises limiting the pump outlet pressure at said pumpoutlet to a first predetermined safety level.
 19. A dynamic method forsetting pump occlusion for an extracorporeal roller pump as claimed inclaim 15, wherein said method further comprises the step of connectingsaid pump inlet and said pump outlet with a second tubing member andmonitoring pump outlet pressure in said second tubing member.
 20. Adynamic method for setting pump occlusion for an extracorporeal rollerpump as claimed in claim 19, wherein said method further comprises thestep of closing said second tubing member below a predetermined pressurewith a pressure relief valve.
 21. A dynamic method for setting theocclusion of an extracorporeal roller pump nonocclusively, said pumphaving a means for adjusting pump occlusion and a first tubing member,said first tubing member having a pump inlet and a pump outlet, saidmethod comprising:(a) determining the expected flow of the pump at afirst predetermined pump speed; (d) determining the net flow of the pumpat said pump outlet with a flowmeter; (e) adjusting the pump occlusionuntil said net flow is at least lower than the flow said expected, thedifference being at least equal to a flow of 5 RPM.
 22. A dynamic methodfor setting the occlusion of an extracorporeal roller pumpnonocclusively, wherein the pump has a motor, a raceway having a racewaydiameter, and at least one roller rotating within said raceway, and afirst pump tubing member is placed in said raceway, said first tubingmember having a tubing inner diameter, a tubing torque, a pump inlet anda pump outlet, said method comprising:(a) at least partially occludingsaid first tubing member with said roller rotating at a first pump speedto pump an extracorporeal fluid therethrough and thereby generating apump inlet and a pump outlet pressure, said pump outlet pressure beingat least a function of said inner diameter, said tubing torque and afirst torque generated by the motor of said roller pump; (b) measuringsaid first torque of said motor; (c) deriving a pressure torque as afunction of said tubing torque and said first torque; (d) calculatingpump outlet pressure as a function of at least said pressure torque,said inner diameter and said raceway diameter; (e) adjusting saidpartial occlusion of said first tubing member to generate a desired pumpoutlet pressure.